Engineering surface epitopes to improve protein crystallization

ABSTRACT

The invention provides for methods and systems for engineering target proteins, based on protein sequence characteristics that influence the likelihood of obtaining a crystal suitable for X-ray structure solution, to improve protein crystallization, as well as related material.

This application is a continuation-in-part of International ApplicationNo. PCT/US2011/33135, filed Apr. 19, 2011, which claims priority to U.S.Provisional Patent Application No. 61/325,723, filed Apr. 19, 2010, U.S.Provisional Patent Application No. 61/432,901, filed Jan. 14, 2011, thecontents of each of which are hereby incorporated by reference in theirentireties.

GOVERNMENT INTERESTS

This invention was made with government support under grants GM074958,GM072867, GM062413, and GM075026 awarded by the National Institutes ofHealth. The government has certain rights in this invention.

This patent disclosure contains material that is subject to copyrightprotection. The copyright owner has no objection to the facsimilereproduction by anyone of the patent document or the patent disclosureas it appears in the U.S. Patent and Trademark Office patent file orrecords, but otherwise reserves any and all copyright rights.

All patents, patent applications and publications cited herein arehereby incorporated by reference in their entirety. The disclosures ofthese publications in their entireties are hereby incorporated byreference into this application in order to more fully describe thestate of the art as known to those skilled therein as of the date of theinvention described herein.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has beensubmitted in ASCII format via EFS-Web and is hereby incorporated byreference in its entirety. Said ASCII copy, created on Jan. 10, 2013, isnamed 192473US.txt and is 1,388,275 bytes in size.

BACKGROUND OF THE INVENTION

Current understanding of biology makes great use of atomic level proteinstructures, but the generation of these structures, e.g., by X-raycrystallography, is both expensive and uncertain. A significantbottleneck in the process is the generation of high quality crystals forX-ray diffraction. Much effort has gone to developing crystallizationscreens, and to creating high-throughput methods for cloning andexpressing proteins (see, e.g., Acton T. B. et al., Methods Enzymol.2005, 394, 210-243). However, the mechanisms of crystallization—and theprotein characteristics that impact it—remain largely unknown and poorlyunderstood, with different methods of study yielding substantiallydifferent results.

The Surface Entropy Reduction (SER) methods, identify mutations that canpotentially improve crystallization by using secondary structureprediction and sequence conservation to locate residues withhigh-entropy side chains in variable loop regions of the protein.Replacing one or more of these residues with a low-entropy amino acid,like alanine, has been predicted to improve crystallization by reducingthe entropic penalty of inter-protein interface formation. Moreover,this approach focuses on making mutations in predicted loop regions ofthe protein's secondary structure.

The methods described herein differ from the SER methods by using theProtein Data Bank (PDB) as a data mine of information to improvepredictions. By using a topological analysis of crystal structures inthe PDB, this is a novel approach to identifying possible mutations toimprove crystallization. The methods described herein are superior asinformation is culled for improving interface formation from interfacesalready experimentally observed. Moreover, unlike the SER methods, themethods and systems described herein use whole epitope modifications,rather than single amino acid changes, thus increasing the success rateat which an inter-protein interface could be formed, since interfacesare usually comprised of a surface and not a single residue interaction.

The epitope modifications involve chemical changes of very diversetypes, including hydrophobic-to-hydrophilic substitutions in equalmeasure to hydrophilic-to-hydrophobic mutations, whereas thesingle-residue mutations suggested by SER involves primarilyhydrophilic-to-hydrophobic substitutions and almost alwayspolarity-reducing mutations. Such mutations tend to impair solubility,which prevents effective protein purification and crystallization. Thegreater diversity in the kinds of chemical changes involved in epitopemodification fundamentally frees crystallization engineering from thecrippling correlation between crystallization-improving andsolubility-impairing mutations. Epitope modifications frequently involveincreasing the side-chain entropy, so they do not require entropyreduction at the level of individual amino acids, which is thefoundation of the SER method.

Finally, SER methods avoid mutations for non-loop regions of theprotein, missing out on many potential epitopes in α-helices, helixcapping motifs, or beta hairpins. The epitope engineering methoddescribed herein includes all secondary structure elements, thusgenerating a larger computational list of possible epitope candidates.

SUMMARY OF THE INVENTION

The invention is based, in part, on the finding that replacement ofcertain epitopes in a protein with more desirable epitopes, some ofwhich occur in non-loop regions of the protein, significantly improvescrystallization properties of the protein for purposes of X-raycrystallographic studies.

It is understood that any of the embodiments described below can becombined in any desired way, and any embodiment or combination ofembodiments can be applied to each of the aspects described below.

In one embodiment, the invention provides for a method of modifying aprotein sequence for high-resolution X-ray crystallographic structuredetermination, the method comprising: (a) receiving a sequence of aprotein of interest; (b) selecting, using a computer, an epitope from anepitope library that is expected to increase the propensity of theprotein of interest to crystallize and that is consistent with sequencevariations observed in homologous proteins; and (c) outputtinginformation on which portion of the amino acid sequence of the proteinof interest should be replaced with the selected epitope to generate amodified protein.

In another embodiment of the invention, the information is outputted inthe form of an amino acid sequence of the modified protein or a portionthereof. In another embodiment of the invention, the information isoutputted in the form of a list of mutations to be made in the aminoacid sequence of the protein of interest to provide the amino acidsequence of the modified protein or a portion thereof. In someembodiments, the information is outputted in the order that is afunction of its likelihood of improving crystallization of the targetprotein.

In some embodiments, the epitope library includes information describingover-representation of an epitope in the PDB database.

In another embodiment of the invention, the method further comprisespredicting the secondary structure of the protein of interest and of itshomolog. In another embodiment, the method further comprises identifyinga homolog of the protein of interest and aligning the sequence of theprotein of interest with the sequence of the homolog.

In one embodiment, the epitope is selected based on one or more of:over-representation P-value for overrepresentation of the epitope in theepitope library; fraction of occurrences of the epitope in the PDBdatabase in crystal-packing contacts; frequency of occurrence of theepitope in crystal-packing interfaces in the PDB database; sequencediversity of proteins containing the epitope in crystal-packinginterfaces in the PDB database; sequence diversity of partner epitopesin the PDB database; low frequency of non-water bridging ligands to theepitope in the PDB database; lack of increase in hydrophobicity of themodified protein by introducing the epitope; or predicted influence ofthe epitope on the solubility of the modified protein.

In another embodiment, the selected epitope is 1-6 amino acid in length.In yet another embodiment, the selected epitope is 2-15 amino acids inlength. In still another embodiment, the selected epitope is 4-15 aminoacids in length. In another embodiment, the selected epitope is 4-6amino acids in length.

In a further embodiment, the epitope includes a polar amino acid. Inanother embodiment of the invention, the selected epitope is an epitopefrom Tables 5-38 (Table 5, in its entirety, discloses SEQ ID NOS118-216, respectively, in order of appearance; Table 6, in its entirety,discloses SEQ ID NOS 217-315, respectively, in order of appearance;Table 7, in its entirety, discloses SEQ ID NOS 316-414, respectively, inorder of appearance; Table 8, in its entirety, discloses SEQ ID NOS415-513, respectively, in order of appearance; Table 9, in its entirety,discloses SEQ ID NOS 514-612, respectively, in order of appearance;Table 10, in its entirety, discloses SEQ ID NOS 613-711, respectively,in order of appearance; Table 11, in its entirety, discloses SEQ ID NOS712-810, respectively, in order of appearance; Table 12, in itsentirety, discloses SEQ ID NOS 811-909, respectively, in order ofappearance; Table 13, in its entirety, discloses SEQ ID NOS 910-1,008,respectively, in order of appearance; Table 14, in its entirety,discloses SEQ ID NOS 1,009-1,107, respectively, in order of appearance;Table 15, in its entirety, discloses SEQ ID NOS 1,108-1,206,respectively, in order of appearance; Table 16, in its entirety,discloses SEQ ID NOS 1,207-1,305, respectively, in order of appearance;Table 17, in its entirety, discloses SEQ ID NOS 1,306-1,404,respectively, in order of appearance; Table 18, in its entirety,discloses SEQ ID NOS 1,405-1,503, respectively, in order of appearance;Table 19, in its entirety, discloses SEQ ID NOS 1,504-1,602,respectively, in order of appearance; Table 20, in its entirety,discloses SEQ ID NOS 1,603-1,701, respectively, in order of appearance;Table 21, in its entirety, discloses SEQ ID NOS 1,702-1,800,respectively, in order of appearance; Table 22, in its entirety,discloses SEQ ID NOS 1,801-1,899, respectively, in order of appearance;Table 23, in its entirety, discloses SEQ ID NOS 1,900-1,998,respectively, in order of appearance; Table 24, in its entirety,discloses SEQ ID NOS 1,999-2,097, respectively, in order of appearance;Table 25, in its entirety, discloses SEQ ID NOS 2,098-2,196,respectively, in order of appearance; Table 26, in its entirety,discloses SEQ ID NOS 2,197-2,295, respectively, in order of appearance;Table 27, in its entirety, discloses SEQ ID NOS 2,296-2,394,respectively, in order of appearance; Table 28, in its entirety,discloses SEQ ID NOS 2,395-2,493, respectively, in order of appearance;Table 29, in its entirety, discloses SEQ ID NOS 2,494-2,592,respectively, in order of appearance; Table 30, in its entirety,discloses SEQ ID NOS 2,593-2,691, respectively, in order of appearance;Table 31, in its entirety, discloses SEQ ID NOS 2,692-2,790,respectively, in order of appearance; Table 32, in its entirety,discloses SEQ ID NOS 2,791-2,889, respectively, in order of appearance;Table 33, in its entirety, discloses SEQ ID NOS 2,890-2,988,respectively, in order of appearance; Table 34, in its entirety,discloses SEQ ID NOS 2,989-3,087, respectively, in order of appearance;Table 35, in its entirety, discloses SEQ ID NOS 3,088-3,186,respectively, in order of appearance). In another embodiment, theselected epitope is an epitope from Tables 2-3. In yet anotherembodiment, the selected epitope is an epitope from other tablesgenerated using equivalent computational approaches to those describedherein with obvious modification consistent with the concepts andprinciples described herein.

In another embodiment, the invention provides for the method where twoor more steps are performed using a computer. In another embodiment, themethod is implemented by a web-based server.

In a further embodiment, the invention provides for generating a nucleicacid sequence encoding a protein comprising the modified protein. Theinvention also provides for a method further comprising expressing themodified protein in a cell or in an in vitro expression system. Inanother embodiment, the method further comprises crystallizing themodified protein of interest.

In one aspect, the invention provides for a system for designing amodified protein for high-resolution X-ray crystallographic structuredetermination, the system comprising a computer having a processor andcomputer-readable program code for performing the method of modifying aprotein sequence for high-resolution X-ray crystallographic structuredetermination, the method comprising: (a) receiving a sequence of aprotein of interest; (b) selecting, using a computer, an epitope from anepitope library that is expected to increase the propensity of theprotein of interest to crystallize and that is consistent with sequencevariations observed in homologous proteins; and (c) outputtinginformation on which portion of the amino acid sequence of the proteinof interest should be replaced with the selected epitope to generate amodified protein.

The invention also provides for a method of using the system to obtainthe amino acid sequence of the modified protein. The invention alsoprovides for a method or a system further comprising generating anucleic acid sequence encoding a protein comprising the modifiedprotein. The invention also provides a method further comprisingexpressing the modified protein in a cell or in an in vitro expressionsystem. In another embodiment, the invention provides for a methodfurther comprising crystallizing the modified protein.

In another aspect, the invention provides for a computer readable mediumcontaining a database of a plurality of epitopes from Tables 2-3 and5-38 (Table 5, in its entirety, discloses SEQ ID NOS 118-216,respectively, in order of appearance; Table 6, in its entirety,discloses SEQ ID NOS 217-315, respectively, in order of appearance;Table 7, in its entirety, discloses SEQ ID NOS 316-414, respectively, inorder of appearance; Table 8, in its entirety, discloses SEQ ID NOS415-513, respectively, in order of appearance; Table 9, in its entirety,discloses SEQ ID NOS 514-612, respectively, in order of appearance;Table 10, in its entirety, discloses SEQ ID NOS 613-711, respectively,in order of appearance; Table 11, in its entirety, discloses SEQ ID NOS712-810, respectively, in order of appearance; Table 12, in itsentirety, discloses SEQ ID NOS 811-909, respectively, in order ofappearance; Table 13, in its entirety, discloses SEQ ID NOS 910-1,008,respectively, in order of appearance; Table 14, in its entirety,discloses SEQ ID NOS 1,009-1,107, respectively, in order of appearance;Table 15, in its entirety, discloses SEQ ID NOS 1,108-1,206,respectively, in order of appearance; Table 16, in its entirety,discloses SEQ ID NOS 1,207-1,305, respectively, in order of appearance;Table 17, in its entirety, discloses SEQ ID NOS 1,306-1,404,respectively, in order of appearance; Table 18, in its entirety,discloses SEQ ID NOS 1,405-1,503, respectively, in order of appearance;Table 19, in its entirety, discloses SEQ ID NOS 1,504-1,602,respectively, in order of appearance; Table 20, in its entirety,discloses SEQ ID NOS 1,603-1,701, respectively, in order of appearance;Table 21, in its entirety, discloses SEQ ID NOS 1,702-1,800,respectively, in order of appearance; Table 22, in its entirety,discloses SEQ ID NOS 1,801-1,899, respectively, in order of appearance;Table 23, in its entirety, discloses SEQ ID NOS 1,900-1,998,respectively, in order of appearance; Table 24, in its entirety,discloses SEQ ID NOS 1,999-2,097, respectively, in order of appearance;Table 25, in its entirety, discloses SEQ ID NOS 2,098-2,196,respectively, in order of appearance; Table 26, in its entirety,discloses SEQ ID NOS 2,197-2,295, respectively, in order of appearance;Table 27, in its entirety, discloses SEQ ID NOS 2,296-2,394,respectively, in order of appearance; Table 28, in its entirety,discloses SEQ ID NOS 2,395-2,493, respectively, in order of appearance;Table 29, in its entirety, discloses SEQ ID NOS 2,494-2,592,respectively, in order of appearance; Table 30, in its entirety,discloses SEQ ID NOS 2,593-2,691, respectively, in order of appearance;Table 31, in its entirety, discloses SEQ ID NOS 2,692-2,790,respectively, in order of appearance; Table 32, in its entirety,discloses SEQ ID NOS 2,791-2,889, respectively, in order of appearance;Table 33, in its entirety, discloses SEQ ID NOS 2,890-2,988,respectively, in order of appearance; Table 34, in its entirety,discloses SEQ ID NOS 2,989-3,087, respectively, in order of appearance;Table 35, in its entirety, discloses SEQ ID NOS 3,088-3,186,respectively, in order of appearance) or other tables generated usingequivalent computational approaches to those described herein. In someembodiments, the computer readable medium contains a database of atleast 100 epitopes from Tables 2-3 and 5-38 (Table 5, in its entirety,discloses SEQ ID NOS 118-216, respectively, in order of appearance;Table 6, in its entirety, discloses SEQ ID NOS 217-315, respectively, inorder of appearance; Table 7, in its entirety, discloses SEQ ID NOS316-414, respectively, in order of appearance; Table 8, in its entirety,discloses SEQ ID NOS 415-513, respectively, in order of appearance;Table 9, in its entirety, discloses SEQ ID NOS 514-612, respectively, inorder of appearance; Table 10, in its entirety, discloses SEQ ID NOS613-711, respectively, in order of appearance; Table 11, in itsentirety, discloses SEQ ID NOS 712-810, respectively, in order ofappearance; Table 12, in its entirety, discloses SEQ ID NOS 811-909,respectively, in order of appearance; Table 13, in its entirety,discloses SEQ ID NOS 910-1,008, respectively, in order of appearance;Table 14, in its entirety, discloses SEQ ID NOS 1,009-1,107,respectively, in order of appearance; Table 15, in its entirety,discloses SEQ ID NOS 1,108-1,206, respectively, in order of appearance;Table 16, in its entirety, discloses SEQ ID NOS 1,207-1,305,respectively, in order of appearance; Table 17, in its entirety,discloses SEQ ID NOS 1,306-1,404, respectively, in order of appearance;Table 18, in its entirety, discloses SEQ ID NOS 1,405-1,503,respectively, in order of appearance; Table 19, in its entirety,discloses SEQ ID NOS 1,504-1,602, respectively, in order of appearance;Table 20, in its entirety, discloses SEQ ID NOS 1,603-1,701,respectively, in order of appearance; Table 21, in its entirety,discloses SEQ ID NOS 1,702-1,800, respectively, in order of appearance;Table 22, in its entirety, discloses SEQ ID NOS 1,801-1,899,respectively, in order of appearance; Table 23, in its entirety,discloses SEQ ID NOS 1,900-1,998, respectively, in order of appearance;Table 24, in its entirety, discloses SEQ ID NOS 1,999-2,097,respectively, in order of appearance; Table 25, in its entirety,discloses SEQ ID NOS 2,098-2,196, respectively, in order of appearance;Table 26, in its entirety, discloses SEQ ID NOS 2,197-2,295,respectively, in order of appearance; Table 27, in its entirety,discloses SEQ ID NOS 2,296-2,394, respectively, in order of appearance;Table 28, in its entirety, discloses SEQ ID NOS 2,395-2,493,respectively, in order of appearance; Table 29, in its entirety,discloses SEQ ID NOS 2,494-2,592, respectively, in order of appearance;Table 30, in its entirety, discloses SEQ ID NOS 2,593-2,691,respectively, in order of appearance; Table 31, in its entirety,discloses SEQ ID NOS 2,692-2,790, respectively, in order of appearance;Table 32, in its entirety, discloses SEQ ID NOS 2,791-2,889,respectively, in order of appearance; Table 33, in its entirety,discloses SEQ ID NOS 2,890-2,988, respectively, in order of appearance;Table 34, in its entirety, discloses SEQ ID NOS 2,989-3,087,respectively, in order of appearance; Table 35, in its entirety,discloses SEQ ID NOS 3,088-3,186, respectively, in order of appearance).In yet another aspect, the invention provides for a computer readablemedium containing information describing over-representation of aplurality of epitopes in the PDB database. In some embodiments, thecomputer readable medium is non-transitory.

In yet another aspect, the invention provides for a recombinant proteinin which a portion of its amino acid sequence has been replaced by anepitope from Tables 2-3 and 5-36 (Table 5, in its entirety, disclosesSEQ ID NOS 118-216, respectively, in order of appearance; Table 6, inits entirety, discloses SEQ ID NOS 217-315, respectively, in order ofappearance; Table 7, in its entirety, discloses SEQ ID NOS 316-414,respectively, in order of appearance; Table 8, in its entirety,discloses SEQ ID NOS 415-513, respectively, in order of appearance;Table 9, in its entirety, discloses SEQ ID NOS 514-612, respectively, inorder of appearance; Table 10, in its entirety, discloses SEQ ID NOS613-711, respectively, in order of appearance; Table 11, in itsentirety, discloses SEQ ID NOS 712-810, respectively, in order ofappearance; Table 12, in its entirety, discloses SEQ ID NOS 811-909,respectively, in order of appearance; Table 13, in its entirety,discloses SEQ ID NOS 910-1,008, respectively, in order of appearance;Table 14, in its entirety, discloses SEQ ID NOS 1,009-1,107,respectively, in order of appearance; Table 15, in its entirety,discloses SEQ ID NOS 1,108-1,206, respectively, in order of appearance;Table 16, in its entirety, discloses SEQ ID NOS 1,207-1,305,respectively, in order of appearance; Table 17, in its entirety,discloses SEQ ID NOS 1,306-1,404, respectively, in order of appearance;Table 18, in its entirety, discloses SEQ ID NOS 1,405-1,503,respectively, in order of appearance; Table 19, in its entirety,discloses SEQ ID NOS 1,504-1,602, respectively, in order of appearance;Table 20, in its entirety, discloses SEQ ID NOS 1,603-1,701,respectively, in order of appearance; Table 21, in its entirety,discloses SEQ ID NOS 1,702-1,800, respectively, in order of appearance;Table 22, in its entirety, discloses SEQ ID NOS 1,801-1,899,respectively, in order of appearance; Table 23, in its entirety,discloses SEQ ID NOS 1,900-1,998, respectively, in order of appearance;Table 24, in its entirety, discloses SEQ ID NOS 1,999-2,097,respectively, in order of appearance; Table 25, in its entirety,discloses SEQ ID NOS 2,098-2,196, respectively, in order of appearance;Table 26, in its entirety, discloses SEQ ID NOS 2,197-2,295,respectively, in order of appearance; Table 27, in its entirety,discloses SEQ ID NOS 2,296-2,394, respectively, in order of appearance;Table 28, in its entirety, discloses SEQ ID NOS 2,395-2,493,respectively, in order of appearance; Table 29, in its entirety,discloses SEQ ID NOS 2,494-2,592, respectively, in order of appearance;Table 30, in its entirety, discloses SEQ ID NOS 2,593-2,691,respectively, in order of appearance; Table 31, in its entirety,discloses SEQ ID NOS 2,692-2,790, respectively, in order of appearance;Table 32, in its entirety, discloses SEQ ID NOS 2,791-2,889,respectively, in order of appearance; Table 33, in its entirety,discloses SEQ ID NOS 2,890-2,988, respectively, in order of appearance;Table 34, in its entirety, discloses SEQ ID NOS 2,989-3,087,respectively, in order of appearance; Table 35, in its entirety,discloses SEQ ID NOS 3,088-3,186, respectively, in order of appearance)or from other tables generated using equivalent computational approachesto those described herein. In still another aspect, the inventionprovides for a crystal of the protein of interest which is obtainedusing the methods of the invention. In one embodiment, the crystal issuitable for high-resolution X-ray crystallographic studies.

In one embodiment, the expression system is an in vitro expressionsystem. In another embodiment, the in vitro expression system is acell-free transcription/translation system. In still another embodiment,the expression system is an in vivo expression system. In yet anotherembodiment, the in vivo expression system is a bacterial expressionsystem or a eukaryotic expression system. In another embodiment, the invivo expression system is an Escherichia coli cell. In still anotherembodiment, the in vivo expression system is a mammalian cell.

In one embodiment, the protein of interest is a human polypeptide, or afragment thereof. In another embodiment, the protein of interest is aviral polypeptide, or a fragment thereof. In another embodiment, theprotein of interest is an antibody, an antibody fragment, an antibodyderivative, a diabody, a tribody, a tetrabody, an antibody dimer, anantibody trimer or a minibody. In another embodiment, the protein ofinterest is a target of pharmaceutical compound or a receptor. In stillanother embodiment, the antibody fragment is a Fab fragment, a Fab′fragment, a F(ab)₂ fragment, a Fd fragment, a Fv fragment, or a ScFvfragment. In yet another embodiment, the protein of interest is acytokine, an inflammatory molecule, a growth factor, a cytokinereceptor, an inflammatory molecule receptor, a growth factor receptor,an oncogene product, or any fragment thereof. In another yet anotherembodiment, the protein of interest is a fusion polypeptide. In oneaspect, the invention described herein relates to a protein of interestproduced by the methods described herein. In one aspect, the inventiondescribed herein relates to a pharmaceutical composition comprising theprotein of interest produced by the methods described herein. In oneaspect, the invention described herein relates to an immunogeniccomposition comprising the protein of interest produced by the methodsdescribed herein.

In one aspect, the invention provides for the use of packing epitopesfrom previously determined X-ray crystal structures in engineering ofproteins with improved crystallization properties.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a diagram of epitope library generation according to oneembodiment of the invention.

FIG. 2 shows characteristics of oligomeric vs. crystal packinginterfaces. Distributions are shown for three levels of interactionclassification: half-interfaces (FIG. 2A, FIG. 2B, and FIG. 2C), fullbinary interaction epitopes (FIG. 2D, FIG. 2E, and FIG. 2F), andelementary binary interaction epitopes (FIG. 2G, FIG. 2H, and FIG. 2I).Distributions show the number of counts of the relevant element binnedby buried surface area (FIG. 2A, FIG. 2D, and FIG. 2G), number ofparticipating residues (FIG. 2B, FIG. 2E, and FIG. 2H), and spread—thenumber of residues, interacting or not, spanned by the element (FIG. 2C,FIG. 2F, and FIG. 2I). Within each graph, separate distributions areshown for all elements, elements which appear in the BioMT database ofinferred biological oligomers, elements which do not appear in BioMT butare within proper interfaces, and elements which do not appear in BioMTand are not proper interfaces. All counts are redundancy-culled.

FIG. 3 is a graphical representation of the analytical scheme forcrystal-packing analysis. Definitions of elements in the packinginterface are given next to schematic depictions of each element. Boldlines represent protein chains, grey lines inter-atomic contacts ≤4 Å,and numbered circles show representative elements.

FIG. 4 shows polymorphism in crystal packing interactions. FIG. 4A:Color-ramped 2-dimensional histogram for 3,185,367 pairs of interfacesfrom crystal structures of proteins with ≥98% sequence identity showingthe percentage of pairwise residue interactions conserved versus the PSS(packing similarity score, defined as the Frobenius product of thecontact or interaction matrices). FIG. 4B: Histogram of PSSs for theseinterfaces calculated either without B-factor weighting (n=0) or withhigh B-factor residues down-weighted (n=3) as described in the text.FIG. 4C: Histogram of unweighted PSSs (packing similarity score, definedas the Frobenius product of the contact or interaction matrices) fornon-proper interfaces formed by proteins with different levels ofsequence identity.

FIG. 5 is a graphical representation of summary statistics on allinterfaces in 39,208 protein crystal structures in the PDB. (A)Histograms showing distributions of the fraction of residuesparticipating in inter-protein packing contacts. (B) Histograms showingnumber of interfaces per crystal. (C) Cumulative distribution graphshowing fraction of interfaces equal to or smaller in size than thenumber indicated on the abscissa. In this graph, residues from the twointeracting molecules are counted separately. The curve labeled“Largest” shows data for the single largest non-proper interface in eachcrystal. (D) Cumulative size and range distributions for hierarchicallydefined packing elements (counting residues from one of the interactingmolecules).

FIG. 6 shows a schematic overview of statistical methods andepitope-engineering software.

FIG. 7 shows a bar graph of the fraction of residues in loops, sheets,and alpha helices that interact in EBIEs. Fractions are shown for allresidues, only residues that are surface-exposed or buried, ascalculated by DSSP, or all residues interacting in BioMT interfacesonly.

FIG. 8 illustrates improvement of crystallization of an integralmembrane protein via epitope engineering. (A) Schematic summary of theresults from a representative initial crystallization screen at 20° C.(B) Micrograph of one well of excellent lead crystals obtained for theMD-to-AG mutant protein in this screen. (C) The same well from awild-type screen conducted in parallel.

FIG. 9 shows epitope-engineering of proteins giving intractablecrystals. FIG. 9 discloses SEQ ID NOS 89-90, 415, 50, 96-97, 50, 99,105, 107-108, 108, 110, 112-113, and 115-117, respectively, in order ofappearance.

FIG. 10 shows the results from preliminary epitope-engineeringexperiments. 36 single epitope mutations were designed in nine proteins.Subsequently, pairs or triplets of these were combined to make fiveproteins bearing multiple epitope mutations. These 41 protein variantsharboring single and multiple epitope mutations were purified andscreened for crystallization using the NESG pipeline. FIG. 10A:Differences in soluble yield in E. coli compared to corresponding WTprotein, as scored on a standard 0-5 scale³³. FIG. 10B: Ratio ofcrystallization stock concentrations compared to WT protein. FIG. 10C:Difference in Thermofluor T_(m) for 30 single mutants. FIG. 10D: Changein number of crystallization hits compared to WT four weeks after set upin the 1536-well robotic screen at the Hauptman-Woodward Institute. FIG.10E: Number of unique crystallization conditions in this screen in whichthe epitope mutant gave a hit while the WT did not. FIG. 10F:Crystal-packing contact involving the mutated F39R residue in the 1.8 Åcrystal structure of NESG target BhR182. FIG. 10F discloses “TxxxxR” asSEQ ID NO: 89.

FIG. 11 A-I shows redundancy-adjusted number of counts for Interface,FBIE, and EBIE.

FIG. 12 shows a solubility comparison of VCR193 single mutants.

FIG. 13 shows a solubility comparison of VCR193 multi mutants.

FIG. 14 shows that epitope mutations open up a new dimension inexploration of crystallization space. The first number in each diagonalcell shows the total number of conditions in which crystals (“hits”)were observed for each protein variant. The numbers in parentheses inthese cells indicate the number of unique chemical conditions givinghits for that variant compared to, first, the WT protein and, second,all other mutant variants evaluated. The off-diagonal cells show thenumber of hit conditions for the variants on the row and the column thatwere not shared with one another (i.e., first for the protein on the rowand second for the one on the column).

FIG. 15 shows the results of an epitope-engineering study on four “nohits” proteins, i.e., proteins that yielded no crystallization hits intwo independent screens of the protein with wild type sequence. Theresults show that crystal structures were solved for two of these fourproteins using 4-5 single eptitope mutations per protein. FIG. 15discloses SEQ ID NOS 5,228-5,231, respectively, in order of appearance.

FIG. 16 shows the structure of epitope-engineered protein LpYceA(LgR82). The eptitope mutation that produced this structure participatesdirectly in a crystal-packing interaction.

FIG. 17 shows “surface-shaping” to calibrate expectations forparticipation in crystal-packing interactions.

FIG. 18 shows that Arg in alpha-helices is the most stronglyoverrepresented amino-acid/secondary-structure class in interfaces inthe PDB.

FIG. 19 shows polar amino acids predominate those most stronglyoverrepresented in interfaces after area-normalization.

DETAILED DESCRIPTION OF THE INVENTION

The issued patents, applications, and other publications that are citedherein are hereby incorporated by reference to the same extent as ifeach was specifically and individually indicated to be incorporated byreference.

Research on the crystallization of proteins substantially predatedefforts to determine their atomic structures using diffraction methods.Despite the historical importance of avidly crystallizing proteins, mostproteins do not produce high-quality crystals. Even for proteins withthe most promising sequence properties, at most ⅓ yield crystalstructures from a single construct. These include the development ofefficacious chemical screens that mimic historically successfulcrystallization conditions, sophisticated robots that enable morecrystallization conditions to be screened with less protein and effort,and numerous innovations that improve crystallization in some cases.However, as long as most proteins cannot be crystallized,crystallization fundamentally remains a hit-or-miss proposition.

Existing methods for improving protein crystallization work with limitedefficiency. Consistent with this premise, changes in primary sequencehave been demonstrated to alter substantially the crystallizationproperties of many proteins. Disordered backbone segments can beidentified using elegant hydrogen-deuterium exchange mass spectrometrymethods, and constructs with such segments excised have shown improvedcrystallization properties. Progressive truncation of the N- andC-termini of the protein can also yield crystallizable constructs ofproteins that initially failed to crystallize. However, many nestedtruncation constructs generally need to be screened, sometimes withtermini differing by as little as two amino acids; even after extensiveeffort, this procedure still frequently fails to yield a soluble proteinconstruct producing high-quality crystals. The Surface Entropy Reduction(SER) method uses site-directed mutagenesis to replace high-entropy sidechains on the surface of the protein (generally lys, glu, and gln) withlower entropy side chains (generally ala). In most cases in which asubstantial improvement in crystallization has been obtained by thismethod, a pair of mutations was introduced at adjacent sites. While somesuccesses have been obtained, most such mutations reduce the solubilityof the protein, frequently so severely that it prevents effectiveprotein purification.

Analyses of large-scale experimental studies show that the surfaceproperties of proteins, and particularly the entropy of the exposed sidechains, are a major determinant of protein crystallization propensity⁴.Such studies demonstrated that overall thermodynamic stability is not amajor determinant of protein crystallization propensity. They alsoidentified a number of primary sequence properties that correlate withcrystallization success, including the fractional content of severalindividual amino acids (i.e., gly, ala, and phe). Equivalent methodshave been used to assess correlations between protein sequenceproperties and expression/solubility results (Price et al., 2011,Microbial Informatics and Experimentation, 1:6,doi:10.1186/2042-5783-1-6). These studies demonstrated that theindividual amino acids that positively correlate with crystallizationsuccess negatively correlate with protein solubility, and vice versa.This effect severely limits the efficacy of single amino acidsubstitutions in improving protein crystallization becausecrystallization probability is low unless starting with a monodispersesoluble protein preparation. Therefore, more sophisticated approachesthan single amino-acid substitutions are needed for efficientengineering of improved protein crystallization.

The methods described herein related to methods for improving proteincrystallization by the introduction of complex sequence epitopes thatmediate high-quality packing contacts in crystal structures depositedinto the Protein Data Bank (PDB).

In certain aspects, the invention relates to the finding that manynaturally occurring proteins have excellent solubility properties andalso crystallize very well. In certain aspects, the invention relates tothe finding specific protein surface epitopes that can mediate stronginterprotein interactions under the conditions that drive proteincrystallization without compromising solubility in the dilute aqueousbuffers used for purification. Described herein are such epitopes aswell as methods for finding such epitopes and using them to engineercrystallization of otherwise crystallization-resistant proteins. Incertain aspects, the invention described herein relates to linearsequence epitopes contributing to interface formation in existingprotein crystal structures. The methods described herein can be used torank the packing quality and potential of these epitopes based onstatistical analyses of epitope prevalence and properties combined withmolecular-mechanics analyses of interfacial and intramolecular packingenergies. Such rankings can be used to prioritize epitopes forsystematic experimental evaluation of their potential to improve thecrystallization properties of otherwise crystallization-resistantproteins.

As used herein, the recitation of a numerical range for a variable isintended to convey that the invention may be practiced with the variableequal to any of the values within that range. Thus, for a variable thatis inherently discrete, the variable can be equal to any integer valuewithin the numerical range, including the end-points of the range.Similarly, for a variable that is inherently continuous, the variablecan be equal to any real value within the numerical range, including theend-points of the range. As an example, and without limitation, avariable which is described as having values between 0 and 2 can takethe values 0, 1 or 2 if the variable is inherently discrete, and cantake the values 0.0, 0.1, 0.01, 0.001, or any other real values ≥0 and≤2 if the variable is inherently continuous.

As used herein, unless specifically indicated otherwise, the word “or”is used in the inclusive sense of “and/or” and not the exclusive senseof “either/or.”

The singular forms “a,” “an,” and “the” include plural references unlessthe content clearly dictates otherwise. Thus, for example, reference to“an epitope” includes a plurality of such epitopes.

An “epitope,” as used herein, is as a specific sequence of amino acidswith a specific secondary-structure pattern that makes intermolecularpacking contacts. The term “epitope” includes a “sub-epitope” which isalso called an “epitope subsequence” herein. In some embodiments, theterm “epitopes” encompasses Elementary Binary Interaction Epitopes(EBIEs).

An “epitope subsequence” or a “sub-epitope”, as used herein, is asequence within an “epitope”, i.e., within a specific pattern of aminoacids with a specific secondary-structure pattern that makesintermolecular packing contacts. For example, the ExxxR (SEQ ID NO:50)/HHHHH epitope subsequence contains Glu and Arg making packingcontacts at positions four residues apart in a continuous segment ofα-helix.

The term “polar amino acid” includes serine (Ser), threonine (Thr),cysteine (Cys), asparagine (Asn), glutamine (Gln), histidine (His),lysine (Lys), arginine (Arg), aspartic acid (Asp), and glutamic acid(Glu).

The term “hydrophobic amino acid” includes glycine (Gly), alanine (Ala),valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro),phenylalanine (Phe), methionine (Met), tryptophan (Trp), and tyrosine(Tyr).

As used herein, EBIE(s) refers to Elementary Binary InteractionEpitope(s), CBIE refers to Continuous Binary Interaction Epitopes(s),and FBIE(s) refers to Full Binary Interaction Epitope(s).

In certain aspects, the methods described herein are based on a newapproach to engineering improved protein crystallization based onintroduction of historically successful crystallization epitopes andsub-epitopes into crystallization-resistant proteins. In certainaspects, the methods described herein relate to the results of datamining high-throughput experimental studies. This analysis showed thatcrystallization propensity is controlled primarily by the prevalence oflow-entropy surface epitopes capable of mediating high-qualitycrystal-packing interactions. The PDB contains an archive of suchepitopes in deposited crystal structures; however, other databases canbe used according to the methods described herein. Computational methodscan be used in connection with the methods described herein to identifyand analyze all crystal-packing epitopes in the PDB. In certain aspects,the invention relates to metrics useful for ranking the efficacy ofpacking epitopes in order to identify those with a high probability offorming energetically favorable interactions under the lowwater-activity conditions used to drive crystallization. For example,such metric can include, but are not limited to statisticalover-representation of each epitope in packing interactions with diversepartner sequences in the PDB. However, other ranking strategies aresuitable for use with the methods described herein, including, but notlimited to, using molecular mechanics calculations to estimateinter-molecular packing energy. In certain aspects, the methodsdescribed herein can be used to engineer the surface of a protein to beenriched in epitopes with favorable packing potential that will promoteformation of a well-ordered 3-dimensional lattice. When the packinginterfaces in some regular lattice have favorable free energy, theformation of that lattice is favored thermodynamically due to theconsistent gain in energy for every added molecule. Thus, in certainaspects the invention described herein relates to the prevalence ofsurface epitopes with high propensity to form such favorableinteractions, which will influence whether a protein can find a latticestructure with favorable intermolecular interactions or whether itprecipitates amorphously with heterogeneous interactions. In certainaspects, the invention relates to the finding that increasing theprevalence of surface epitopes with favorable packing potentialincreases high quality crystallization.

Generation of a Library of Epitopes that are Expected to ImproveCrystallization Properties of a Target Protein

In some embodiments, a database is generated containing a library of allelementary, continuous, or full binary interaction epitopes (EBIEs,CBIEs, and FBIEs) in the PDB that span at most two successive regularsecondary structural elements and flanking loops (as identified by theDSSP algorithm (Kabsch and Sander, Dictionary of protein secondarystructure: pattern recognition of hydrogen-bonded and geometricalfeatures. Biopolymers 22 (12), 2577-637 (1983)).

An interface is defined as all residues making atomic contacts (≤4 Å)between two protein molecules related by a single rotation-translationoperation in the real-space crystal lattice. The interface is decomposedinto features called Elementary Binary Interaction Epitopes (EBIEs).These comprise a connected set of residues that are covalently bonded ormake van der Waals interactions to one other in one molecule and thatalso contact a similarly connected set of residues in the other moleculeforming the interface. EBIEs can be the foundation of this analysisbecause these features and their constituent sub-features representpotentially engineerable sequence motifs. One or more EBIEs that areconnected to one another by covalent bonds or van der Waals interactionswithin a molecule form a Continuous Binary Interaction Epitope (CBIE).One or more CBIEs in one molecule that are connected to one anotherindirectly by a chain of contacts across a single interface form a FullBinary Interaction Epitope (FBIE). The set of one or more FBIEs that allmediate contacts between the same two molecules in the real-spacelattice form a complete interface.

The sequence of both contacting and non-contacting residues is storedalong with the standard DSSP-encoding of the secondary structure at eachposition in the protein structure in which the epitope was observed tomediate a crystal-packing interaction. All metrics possibly related tothe crystal-packing potential of the epitope are recorded, includingB-factor distribution parameters, statistical enrichment scores relativeto all interfaces in the PDB, as well as conservation in multiplecrystals from homologous proteins, and crystallization propensity andsolubility scores based on the sequence composition of the epitope. Thedatabase includes the identity of all EBIE pairs making contact witheach other as well as a breakdown of the composition of all FBIEs andCBIEs in terms of their constituent EBIEs. This versatile resource foranalyzing and engineering crystallization epitopes is available on thecrystallization engineering web-server.

One embodiment of the invention which demonstrates how an epitopelibrary can be generated is schematized in FIG. 1. A hierarchicalanalytical scheme has been developed to identify contiguous epitopespotentially useful for protein engineering, and has been used to analyzeall inter-protein packing interactions in crystal structures in the PDB.The hierarchical scheme can be very useful for this analysis.

The PDB contain some structures that have errors which createsinaccuracies in the characterization of these structures. It alsocontains many structures that are partially or completely redundant thatcreate problems in the eventual identification of sequence motifs thatare over-represented in crystal-packing interactions. These concerns canbe addressed by computational flagging and down-weighting mechanisms,respectively.

Biological and non-biological protein oligomers can be addressed asfollows. To identify biological oligomers, the BioMT database (Krissineland Henrick, Inference of macromolecular assemblies from crystallinestate. J. Mol. Biol. 372, 774-797), which attempts to categorize allpreviously described biological interfaces in the PDB, can be used.Interfaces so identified are flagged as “BioMT” interfaces. Recognizingthat some oligomeric interfaces may not be appropriately categorized byBioMT, the set of “proper” interfaces which could be either biologicalor crystallographic are identified.

Interfaces are designated as “proper” if they form part of a regularoligomer with proper rotational symmetry (i.e., n protein molecules inthe real-space lattice each related to the next by a 360°/n rotation±5°,with n being any integer from 2-12) and “non-proper” if they do not.Proper interfaces could potentially be part of a stable physiologicaloligomer while non-proper interfaces cannot. After these twocategorization steps, four sets of interfaces exist: the set of allinterfaces; the set of biological interfaces identified by BioMT; theset of proper interfaces not identified as biological interfaces byBioMT, but which could potentially be either biological orcrystallographic; and the set of interfaces which are not identified byBioMT and which are not proper, as defined above. The most conservativeapproach to isolating non-physiological crystal-packing interactions isto focus exclusively on non-proper interfaces in order to exclude anycomplex that is potentially a physiological oligomer. Nonetheless,epitopes that contribute to stabilizing physiological oligomers maystill be useful for engineering purposes, and epitopes that promoteformation of a regular oligomer would be particularly useful becausestable oligomerization strongly promotes crystallization (Price et al.,Understanding the physical properties that control proteincrystallization by analysis of large-scale experimental data. NatBiotechnol 27 (1), 51-7 (2009)).

FIG. 2 illustrates characteristics of oligomeric vs. crystal-packinginterfaces. Distributions are shown for three levels of interactionclassification: half-interfaces (A, B, and C), full binary interactionepitopes (D, E, and F), and elementary binary interaction epitopes (G,H, and I). Distributions show the number of counts of the relevantelement binned by buried surface area (A, D, and G), number ofparticipating residues (B, E, and H), and spread—the number of residues,interacting or not, spanned by the element (C, F, and I). Within eachgraph, separate distributions are shown for all elements, elements whichappear in the BioMT database of biological oligomers, elements which donot appear in BioMT but are within proper interfaces (as defined above),and elements which do not appear in BioMT and are not proper interfaces.All counts are redundancy-culled as described below. PSS is the PackingSimilarity Score, and can be calculated as discussed further below.

One approach to redundancy reduction of epitope counts is describedherein. Starting with all interfaces (FIG. 3) found in the analyzed setof 39,208 crystal structures, select all non-pathological proteincrystals based on exclusion of those with pathologically closeintermolecular packing.

Cull-1: Select non-redundant crystals: PSS<0.5 for any pair of crystals(comparing all chains).

Cull-2: Select non-BioMT interfaces, i.e., not related by PDB-designatedBioMT transformation.

Cull-3: Select non-redundant interfaces within each crystal, i.e., withPSS<0.5 for any pair of interfaces within each crystal.

Cull-3′: Select non-redundant interfaces between crystals, i.e., withPSS<0.5 for any pair of interfaces included in the analyses, even thosein different crystals.

Count unique chain sequences contributing to Cull-3 at the 25% identitylevel (i.e., the number of protein chains without any pair havinggreater than or equal to 25% identity to one another).

Even when all biological and oligomeric interfaces are removed from thedataset, significant redundancy remains within the PDB. Many proteins inthe PDB have had multiple crystal structures deposited, which may havevery similar if not identical packing interactions (e.g., multiplemutations at a non-interacting active site) but which can also havecompletely separate packing interactions (e.g., crystallization underdifferent conditions into a different crystal form). Simply cullingidentical or homologous proteins would remove all redundancy but wouldalso eliminate significant information from the second situation, wherethe same protein forms crystals with different packing interactions.

To implement a redundancy down-weighting, the Packing Similarity Score(PSS) has been developed to evaluate the similarity betweeninter-protein interfaces, full chain interactions, and crystals. PSS canbe calculated in the following way: Interactions matrices are generatedfor each interface, with rows representing residues in one chain andcolumns representing residues in the other chain. Cells in the matrixinclude the number of inter-atomic contacts between the two residues(including contacts mediated by a single solvent molecule) and theB-factor-derived weight associated with that contact. The PSS betweentwo interfaces is defined as the normalized Frobenius product (a matrixdot-product) of the two interaction matrices, which are aligned to oneanother based on standard methods for aligning homologous proteinsequences, as described below. The PSS takes values in the range between0 and 1. This value contains significant information about the overallsimilarity of two interfaces, and is sensitive to small changes (FIG.4A). To calculate the PSS for two chains or two crystals, the process isessentially repeated on a larger scale. Each interface in one chain ismatched with an interface in the second chain with which it has thehighest PSS. Interfaces are ordered in this way, and the individualinteraction matrices are then inscribed into the larger chain/chain orcrystal/crystal interaction matrix. The Frobenius product of this matrixis then taken. However, since best-matches are not necessarilyreciprocal, the best-interface-matching process is repeated in reverseto ensure reciprocity of the chain or crystal PSS. The Frobeniusproducts of the two matrices are added and then normalized to give thechain or crystal PSS.

Each interface in a crystal structure is quantitatively described by acontact matrix C containing the corresponding C_(u) values (i.e., withits rows and columns indexed by the residue numbers in the twointeraction proteins). To evaluate the similarity in inter-proteininterfaces formed by homologous proteins, their sequences are alignedusing CLUSTAL-W (Higgins et al., Using CLUSTAL for multiple sequencealignments. Methods in Enzymology 266, 383-402 (1996)) aftertransitively grouping together all proteins sharing at least 25%sequence identity. This procedure effectively aligns both the columnsand rows in the contact matrices for interfaces formed by the homologousproteins. The Packing Similarity Score (PSS) between the interfaces isthen calculated as the Frobenius (matrix-direct) product between therespective contact matrices. This procedure is mathematically equivalentto calculating a dot-product between vectors filled with the contactcount between corresponding residue pairs in homologous interfaces. PSSvalues range from 1.0, if the number of contacts between eachinterfacial residue pair is identical, to 0.0, if no pair-wise contactsare preserved.

FIG. 5 shows statistics from application of the analytical scheme shownin FIG. 3 to all crystal structures in the PDB (39,208 entries). Theaverage number of total, proper, and non-proper interfaces per proteinmolecular are 6.9, 1.8, and 5.1, respectively (FIG. 5A). While a minimumof four interfaces is required for a single molecule to form a3-dimensional lattice, fewer are possible when multiple molecules arepresent in the crystallographic asymmetric unit. Proteins generallycontain only a small number of interfaces beyond the minimum requiredfor lattice formation, indicating that most interfaces contribute tostructural stabilization of the lattice. On average, 50% ofsurface-exposed residues and 36% of all residues participate ininter-protein packing interactions (FIG. 5B). While interfaces rangewidely in size, 36% of all interfaces and 42% of non-proper interfacescontain 10 or fewer residues counting contributions from both sides ofthe interface (˜5 from each participating molecule) (FIG. 5C). The smallsize of the average interface is encouraging relative to the feasibilityof engineering interface formation. Half of all interfaces are undereight residues in size, and a quarter (8678 total in the datasetanalyzed herein) are under eight residues in range within thepolypeptide chain (separation). The cumulative size/range distributionsfor all interfaces, CBIEs, and EBIEs (FIG. 5D) shows that mostinterfaces are topologically simple and local in the primary sequence,even though some are complex. It is noteworthy that FBIEs contain onaverage fewer than two EBIEs and that most EBIEs are less than 4residues in size and 10 residues in range. These small EBIEs representprime candidates for engineering improved crystallization ofcrystallization-resistant proteins.

The epitope library was used to count all EBIEs that appear in the PDB,and to determine which sequences are statistically over-represented inEBIEs given their background frequency in non-interacting sequences inthe PDB. Before specific amino acid sequences were considered, thesecondary structure patterns that appeared most frequently in EBIEs wereexamined. Some secondary structure patterns appeared much morefrequently than others; these are summarized in Table 1.

TABLE 1 SECONDARY STRUCTURE MOTIFS IN EBIEs^(a) Null Secondary FractionFraction Probability Probability Size Structure in PDB in EBIEs in EBIEin EBIE Z Score P-value* 1 C 0.41 0.510 0.357 0.33 85.2 0 1 H 0.36 0.3320.321 0.33 −33.8 3.21E−251 1 E 0.23 0.159 0.290 0.33 −91.3 0 2 CC 0.320.481 0.171 0.15 101.5 0 2 HC 0.036 0.048 0.168 0.15 29.1 1.51E−186 2 CH0.035 0.042 0.154 0.15 9.5 6.95E−22 2 EC 0.049 0.042 0.151 0.15 4.87.29E−07 2 CE 0.050 0.046 0.144 0.15 −4.2 1.65E−05 2 HE 0.0016 0.000610.118 0.15 −5.5 2.70E−08 2 EH 0.0029 0.0012 0.091 0.15 −16.9 5.60E−64 2EE 0.184 0.106 0.134 0.15 −31.3 1.84E−215 2 HH 0.320 0.232 0.116 0.15−113.7 0 3 HCC 0.031 0.051 0.096 0.076 35.8 2.51E−280 3 CCH 0.029 0.0420.094 0.076 30.4 1.10E−203 3 CCC 0.245 0.436 0.094 0.076 98.0 0 3 CHH0.035 0.057 0.092 0.076 31.2 1.42E−214 3 ECC 0.043 0.052 0.090 0.07627.2 1.33E−162 4 HCCH 0.0025 0.0040 0.057 0.042 9.4 4.30E−21 4 HCHH0.0026 0.0044 0.057 0.042 9.6 4.55E−22 4 HCCC 0.026 0.046 0.056 0.04230.0 7.12E−198 4 CCCH 0.023 0.039 0.056 0.042 27.3 2.22E−164 4 CECH0.00083 0.00077 0.055 0.042 3.7 0.000142 ^(a)Table 1 shows the secondarystructure motifs (coil [C], strand [E], or helix [H]) mostover-represented in EBIEs. Full distributions are shown for sequences oflength 1 and 2, and the 5 most over-represented (and statisticallysignificant) sequences of length 3 and 4. The table shows the frequencyof that motif in the PDB generally, the frequency in EBIEs, theprobability of any given instance of that motif participating in anEBIE, the null probability of any sequence of that length participatingin an EBIE, and the Z-score and P-value of that over- orunder-representation. All calculations were done on the weighted set ofchains. *P-values denoted 0 fell below the computational threshold ofMicrosoft Excel, and are therefore less than 10⁻³⁰⁰.

Next, amino acid sequences which appear as subsequences within EBIEs(e.g., an interacting trimer which makes up only part of an EBIE) wereconsidered. Due to computational restrictions, the statistical analysiswas only performed on dimers, trimers, and tetramers. Many of theseshort amino acid sequences are significantly over-represented in the setof EBIEs (Table 2).

TABLE 2 TOP SEQUENCE MOTIFS IN EBIEs, IGNORING SECONDARY STRUCTURE.^(a)(SEQ ID NOS 12-26, respectively, in order of appearance) Null Fractionin Fraction in Probability Probability Size Sequence PDB EBIEs in EBIEin EBIE Z Score P-value* 2 HH 0.00109 0.00032 0.30 0.15 32.9 5.43E−238 2WC 9.48E−05 2.26E−05 0.24 0.15 5.9 2.10E−09 2 CH 0.00037 8.04E−05 0.220.15 9.1 6.03E−20 2 HM 0.00051 0.00011 0.21 0.15 10.2 8.33E−25 2 CS0.00070 0.00015 0.21 0.15 11.1 4.95E−29 3 SCW 5.35E−06 4.69E−06 0.880.076 16.6 1.01E−25 3 HHH 0.00033 0.00011 0.33 0.076 42.3 0 3 WCG1.87E−05 6.26E−06 0.33 0.076 10.0 3.96E−23 3 SHM 8.78E−05 2.29E−05 0.260.076 15.6 2.13E−54 3 VAC 3.48E−05 8.11E−06 0.23 0.076 8.3 1.32E−16 4CSAG 1.55E−05 6.55E−11 1.26 0.042 21.8 1.56E−29 4 TQWC 1.79E−06 7.58E−120.98 0.042 11.5 7.42E−09 4 HCGV 5.29E−06 2.23E−11 0.80 0.042 12.35.04E−10 4 ACNG 2.96E−06 1.25E−11 0.80 0.042 11.1 6.40E−09 4 DACQ 6.9E−06 2.92E−11 0.79 0.042 12.6 4.18E−11 ^(a)Table 2 shows the aminoacid sequences most over-represented in EBIEs, ignoring secondarystructure. The top five most over-represented (and statisticallysignificant) examples are shown for sequences of length 2, 3, and 4. Thetable shows the frequency of that motif in the PDB generally (weightedby surface-interior proclivity to match the surface-interiordistribution of EBIEs, as described above), the frequency in EBIEs, theprobability of any given instance of that motif participating in anEBIE, the null probability of any sequence of that length participatingin an EBIE, and the Z-score and P-value of that over- orunder-representation. All calculations were done on the weighted set ofchains. *P-values denoted 0 fell below the computational threshold ofMicrosoft Excel, and are therefore less than 10⁻³⁰⁰.

Finally, it was determined which complete EBIE sequences appearedsignificantly more frequently than their background frequency wouldsuggest (Table 3).

TABLE 3 TOP SEQUENCE MOTIFS IN EBIEs, INCLUDING SECONDARY STRUCTURE.^(a)(SEQ ID NOS 27-41, respectively, in order of appearance) Null SecondaryFraction Fraction in Probability Probability Size Sequence Structure inPDB EBIEs in EBIE in EBIE Z Score P-value* 2 CW H  2.2E−05 1.01E−05 0.460.15 9.8 1.59E−22 2 HH CC 0.00060 0.00023 0.38 0.15 39.0 0 2 WC CC3.75E−05 1.37E−05 0.37 0.15 9.0 3.82E−19 2 HM CC 0.00022 7.21E−05 0.320.15 17.5 2.31E−68 2 GK CH 0.00029 8.05E−05 0.28 0.15 14.8 2.31E−49 3PTW CEE 2.17E−06 2.35E−06 1.08 0.076 12.2 5.03E−14 3 CAT ECC 1.94E−061.96E−06 1.01 0.076 11.5 5.15E−12 3 VAC ECC 7.11E−06 7.16E−06 1.01 0.07622.1 5.11E−44 3 GSC CCH 3.19E−06 2.96E−06 0.93 0.076 13.6 5.11E−17 3 VGKCCH 1.56E−05 1.33E−05 0.85 0.076 27.5 4.72E−164 4 AGKT CCHH 1.43E−056.04E−11 2.12 0.042 19.6 5.89E−24 4 VGKS CCHH 2.49E−05 1.05E−10 1.390.042 27.5 1.88E−45 4 GNLA CCCE 1.97E−06 8.33E−12 1.33 0.042 13.03.81E−10 4 QGLG CCHH  1.2E−06 5.08E−12 1.33 0.042 11.6 5.84E−09 4 AAGKCCCH 5.92E−06  2.5E−11 1.31 0.042 16.9 6.53E−17 ^(a)Table 3 shows theamino acid sequences most over-represented in EBIEs, consideringsecondary structure. The top five most over-represented (andstatistically significant) examples are shown for sequences of length 2,3, and 4, where the sequence is considered to be the combination ofresidue identity and secondary structure (coil [C], strand [E], or helix[H]) for that position, as calculated by DSSP. The table shows thefrequency of that motif in the PDB generally (weighted bysurface-interior proclivity to match the surface-interior distributionof EBIEs, as described above), the frequency in EBIEs, the probabilityof any given instance of that motif participating in an EBIE, the nullprobability of any sequence of that length participating in an EBIE, andthe Z-score and P-value of that over- or under-representation. Allcalculations were done on the weighted set of chains. *P-values denoted0 fell below the computational threshold of Microsoft Excel, and aretherefore less than 10⁻³⁰⁰.

As of the time of the analysis presented herein, among the PDB proteinchains there were 54,317,358 potential epitope subsequences of length 1to 6. The substrings describe primary and secondary structure and are offorms like FxGH (SEQ ID NO: 539) CcCH, i.e., intermediate amino acidletters masked by x's are ignored but their secondary structure is stillconsidered. There are 31 such masks total. Not every possiblepermutation of 20 amino acids and 3 structure codes among the 31 masks(57,625,347,600 total) is found in the PDB. Accordingly, 54,317,358 isthe number of independent trials for purposes of Bonferroni correctionfor multiple-hypothesis testing. Therefore, the 5% significancethreshold becomes 9.205e-10 after dividing by the number of independenttests.

In some embodiments, all epitope subsequences that make up the finallibrary have an over-representation-in-interfaces P-value below theafore mentioned significance threshold. In some embodiments, thesequence's redundancy-weighted “in epitopes” and “in prior” counts areat least 10 (in order to deprioritize the few epitopes with very lowcounts that still manage to remain significant). In some embodiments,the fraction of redundancy-corrected occurrences of the epitope havingnon-water bridging solvent molecules is no more than 50% of the totalsuch count, and the sequence's over-representation ratio(redundancy-corrected count in epitopes/expected redundancy-correctedcount in epitopes) is at least 1.5. The number of epitopes that meetthese four criteria is 2,040. They make up one embodiment of an epitopesubsequence library for use in crystallization engineering.

Tables 4-35 (Table 5, in its entirety, discloses SEQ ID NOS 118-216,respectively, in order of appearance; Table 6, in its entirety,discloses SEQ ID NOS 217-315, respectively, in order of appearance;Table 7, in its entirety, discloses SEQ ID NOS 316-414, respectively, inorder of appearance; Table 8, in its entirety, discloses SEQ ID NOS415-513, respectively, in order of appearance; Table 9, in its entirety,discloses SEQ ID NOS 514-612, respectively, in order of appearance;Table 10, in its entirety, discloses SEQ ID NOS 613-711, respectively,in order of appearance; Table 11, in its entirety, discloses SEQ ID NOS712-810, respectively, in order of appearance; Table 12, in itsentirety, discloses SEQ ID NOS 811-909, respectively, in order ofappearance; Table 13, in its entirety, discloses SEQ ID NOS 910-1,008,respectively, in order of appearance; Table 14, in its entirety,discloses SEQ ID NOS 1,009-1,107, respectively, in order of appearance;Table 15, in its entirety, discloses SEQ ID NOS 1,108-1,206,respectively, in order of appearance; Table 16, in its entirety,discloses SEQ ID NOS 1,207-1,305, respectively, in order of appearance;Table 17, in its entirety, discloses SEQ ID NOS 1,306-1,404,respectively, in order of appearance; Table 18, in its entirety,discloses SEQ ID NOS 1,405-1,503, respectively, in order of appearance;Table 19, in its entirety, discloses SEQ ID NOS 1,504-1,602,respectively, in order of appearance; Table 20, in its entirety,discloses SEQ ID NOS 1,603-1,701, respectively, in order of appearance;Table 21, in its entirety, discloses SEQ ID NOS 1,702-1,800,respectively, in order of appearance; Table 22, in its entirety,discloses SEQ ID NOS 1,801-1,899, respectively, in order of appearance;Table 23, in its entirety, discloses SEQ ID NOS 1,900-1,998,respectively, in order of appearance; Table 24, in its entirety,discloses SEQ ID NOS 1,999-2,097, respectively, in order of appearance;Table 25, in its entirety, discloses SEQ ID NOS 2,098-2,196,respectively, in order of appearance; Table 26, in its entirety,discloses SEQ ID NOS 2,197-2,295, respectively, in order of appearance;Table 27, in its entirety, discloses SEQ ID NOS 2,296-2,394,respectively, in order of appearance; Table 28, in its entirety,discloses SEQ ID NOS 2,395-2,493, respectively, in order of appearance;Table 29, in its entirety, discloses SEQ ID NOS 2,494-2,592,respectively, in order of appearance; Table 30, in its entirety,discloses SEQ ID NOS 2,593-2,691, respectively, in order of appearance;Table 31, in its entirety, discloses SEQ ID NOS 2,692-2,790,respectively, in order of appearance; Table 32, in its entirety,discloses SEQ ID NOS 2,791-2,889, respectively, in order of appearance;Table 33, in its entirety, discloses SEQ ID NOS 2,890-2,988,respectively, in order of appearance; Table 34, in its entirety,discloses SEQ ID NOS 2,989-3,087, respectively, in order of appearance;Table 35, in its entirety, discloses SEQ ID NOS 3,088-3,186,respectively, in order of appearance) (in Appendix A) provide a list of100 top patterns (engineering candidates) for epitopes in each of 32interaction pattern classes. Column “Sequence” provides the amino acidsequence of the epitope subsequence (Tables 5-35 (Table 5, in itsentirety, discloses SEQ ID NOS 118-216, respectively, in order ofappearance; Table 6, in its entirety, discloses SEQ ID NOS 217-315,respectively, in order of appearance; Table 7, in its entirety,discloses SEQ ID NOS 316-414, respectively, in order of appearance;Table 8, in its entirety, discloses SEQ ID NOS 415-513, respectively, inorder of appearance; Table 9, in its entirety, discloses SEQ ID NOS514-612, respectively, in order of appearance; Table 10, in itsentirety, discloses SEQ ID NOS 613-711, respectively, in order ofappearance; Table 11, in its entirety, discloses SEQ ID NOS 712-810,respectively, in order of appearance; Table 12, in its entirety,discloses SEQ ID NOS 811-909, respectively, in order of appearance;Table 13, in its entirety, discloses SEQ ID NOS 910-1,008, respectively,in order of appearance; Table 14, in its entirety, discloses SEQ ID NOS1,009-1,107, respectively, in order of appearance; Table 15, in itsentirety, discloses SEQ ID NOS 1,108-1,206, respectively, in order ofappearance; Table 16, in its entirety, discloses SEQ ID NOS 1,207-1,305,respectively, in order of appearance; Table 17, in its entirety,discloses SEQ ID NOS 1,306-1,404, respectively, in order of appearance;Table 18, in its entirety, discloses SEQ ID NOS 1,405-1,503,respectively, in order of appearance; Table 19, in its entirety,discloses SEQ ID NOS 1,504-1,602, respectively, in order of appearance;Table 20, in its entirety, discloses SEQ ID NOS 1,603-1,701,respectively, in order of appearance; Table 21, in its entirety,discloses SEQ ID NOS 1,702-1,800, respectively, in order of appearance;Table 22, in its entirety, discloses SEQ ID NOS 1,801-1,899,respectively, in order of appearance; Table 23, in its entirety,discloses SEQ ID NOS 1,900-1,998, respectively, in order of appearance;Table 24, in its entirety, discloses SEQ ID NOS 1,999-2,097,respectively, in order of appearance; Table 25, in its entirety,discloses SEQ ID NOS 2,098-2,196, respectively, in order of appearance;Table 26, in its entirety, discloses SEQ ID NOS 2,197-2,295,respectively, in order of appearance; Table 27, in its entirety,discloses SEQ ID NOS 2,296-2,394, respectively, in order of appearance;Table 28, in its entirety, discloses SEQ ID NOS 2,395-2,493,respectively, in order of appearance; Table 29, in its entirety,discloses SEQ ID NOS 2,494-2,592, respectively, in order of appearance;Table 30, in its entirety, discloses SEQ ID NOS 2,593-2,691,respectively, in order of appearance; Table 31, in its entirety,discloses SEQ ID NOS 2,692-2,790, respectively, in order of appearance;Table 32, in its entirety, discloses SEQ ID NOS 2,791-2,889,respectively, in order of appearance; Table 33, in its entirety,discloses SEQ ID NOS 2,890-2,988, respectively, in order of appearance;Table 34, in its entirety, discloses SEQ ID NOS 2,989-3,087,respectively, in order of appearance; Table 35, in its entirety,discloses SEQ ID NOS 3,088-3,186, respectively, in order of appearance))or of a single amino acid (Table 4). Lower case ‘x’ means that that theamino acid identity of the residue at that position has not beenexplicitly considered. Column “Structure” shows the observed secondarystructure motifs (loop or coil [C], beta strand [E], or helix [H]) ofthe pattern. All measured frequencies of occurrence wereredundancy-corrected. Column “In Epitopes” represents the observednumber of occurrences of each epitope in the PDB. Column “Expected inEpi” represents the expected number of each epitope in crystal-packinginterfaces in the PDB. Column “In PDB” represents the total number oftimes the epitope's sequence appears in the PDB, regardless of whetheror not it participates in interactions. Column “Z-score” represents thenumber of standard deviations that the observed count is away from theexpected count. P-values represent the upper and the lower tailintegrals of the binomial distribution. Column “Distribution” representswhether the distribution is approximated as normal (N) or as exactbinomial (B). The “Observed ratio” is the fraction of “In PDB” thatactually makes crystal-packing contacts. “Null probability” is thefraction of “In PDB” expected in crystal-packing epitopes. Allcalculations were done on the weighted set of chains. *—P-values denoted0 fell below the lowest floating point precision value, and aretherefore at least less than 10⁻³⁰⁰.

Table 36 (in Appendix A) provides a list of epitopes subsequencesaccording to some embodiments of the invention. In Table 36, “NumCrystal Sets” is the number of crystals in the PDB containing theepitope subsequence after correction for redundancy in overall packingusing PSS. “Num Interface Intersets” is the number of interfaces in thePDB containing the epitope subsequence after correction for redundancyin overall packing using PSS. “Num Chainsets 25” is the number ofsequence-unique proteins (<25% identity between any pair) in the PDBcontaining the epitope subsequence. “Non-Water Solvent” is the fractionof epitopes containing the epitope subsequence whose contacts to thepartner epitope across the crystal-packing interface involve bridginginteractions via ligands bound to the protein or via small moleculesfrom the crystallization solution other than water. The details forTable 37 is provided further below.

Surprisingly, many epitopes in Tables 2-3 and 5-37 (Table 5, in itsentirety, discloses SEQ ID NOS 118-216, respectively, in order ofappearance; Table 6, in its entirety, discloses SEQ ID NOS 217-315,respectively, in order of appearance; Table 7, in its entirety,discloses SEQ ID NOS 316-414, respectively, in order of appearance;Table 8, in its entirety, discloses SEQ ID NOS 415-513, respectively, inorder of appearance; Table 9, in its entirety, discloses SEQ ID NOS514-612, respectively, in order of appearance; Table 10, in itsentirety, discloses SEQ ID NOS 613-711, respectively, in order ofappearance; Table 11, in its entirety, discloses SEQ ID NOS 712-810,respectively, in order of appearance; Table 12, in its entirety,discloses SEQ ID NOS 811-909, respectively, in order of appearance;Table 13, in its entirety, discloses SEQ ID NOS 910-1,008, respectively,in order of appearance; Table 14, in its entirety, discloses SEQ ID NOS1,009-1,107, respectively, in order of appearance; Table 15, in itsentirety, discloses SEQ ID NOS 1,108-1,206, respectively, in order ofappearance; Table 16, in its entirety, discloses SEQ ID NOS 1,207-1,305,respectively, in order of appearance; Table 17, in its entirety,discloses SEQ ID NOS 1,306-1,404, respectively, in order of appearance;Table 18, in its entirety, discloses SEQ ID NOS 1,405-1,503,respectively, in order of appearance; Table 19, in its entirety,discloses SEQ ID NOS 1,504-1,602, respectively, in order of appearance;Table 20, in its entirety, discloses SEQ ID NOS 1,603-1,701,respectively, in order of appearance; Table 21, in its entirety,discloses SEQ ID NOS 1,702-1,800, respectively, in order of appearance;Table 22, in its entirety, discloses SEQ ID NOS 1,801-1,899,respectively, in order of appearance; Table 23, in its entirety,discloses SEQ ID NOS 1,900-1,998, respectively, in order of appearance;Table 24, in its entirety, discloses SEQ ID NOS 1,999-2,097,respectively, in order of appearance; Table 25, in its entirety,discloses SEQ ID NOS 2,098-2,196, respectively, in order of appearance;Table 26, in its entirety, discloses SEQ ID NOS 2,197-2,295,respectively, in order of appearance; Table 27, in its entirety,discloses SEQ ID NOS 2,296-2,394, respectively, in order of appearance;Table 28, in its entirety, discloses SEQ ID NOS 2,395-2,493,respectively, in order of appearance; Table 29, in its entirety,discloses SEQ ID NOS 2,494-2,592, respectively, in order of appearance;Table 30, in its entirety, discloses SEQ ID NOS 2,593-2,691,respectively, in order of appearance; Table 31, in its entirety,discloses SEQ ID NOS 2,692-2,790, respectively, in order of appearance;Table 32, in its entirety, discloses SEQ ID NOS 2,791-2,889,respectively, in order of appearance; Table 33, in its entirety,discloses SEQ ID NOS 2,890-2,988, respectively, in order of appearance;Table 34, in its entirety, discloses SEQ ID NOS 2,989-3,087,respectively, in order of appearance; Table 35, in its entirety,discloses SEQ ID NOS 3,088-3,186, respectively, in order of appearance)include polar residues. Epitopes with polar residues are advantageous asthey are less likely to cause the modified protein to become insoluble.

In some embodiments, the epitope library comprises the epitopes inTables 5-37 (Table 5, in its entirety, discloses SEQ ID NOS 118-216,respectively, in order of appearance; Table 6, in its entirety,discloses SEQ ID NOS 217-315, respectively, in order of appearance;Table 7, in its entirety, discloses SEQ ID NOS 316-414, respectively, inorder of appearance; Table 8, in its entirety, discloses SEQ ID NOS415-513, respectively, in order of appearance; Table 9, in its entirety,discloses SEQ ID NOS 514-612, respectively, in order of appearance;Table 10, in its entirety, discloses SEQ ID NOS 613-711, respectively,in order of appearance; Table 11, in its entirety, discloses SEQ ID NOS712-810, respectively, in order of appearance; Table 12, in itsentirety, discloses SEQ ID NOS 811-909, respectively, in order ofappearance; Table 13, in its entirety, discloses SEQ ID NOS 910-1,008,respectively, in order of appearance; Table 14, in its entirety,discloses SEQ ID NOS 1,009-1,107, respectively, in order of appearance;Table 15, in its entirety, discloses SEQ ID NOS 1,108-1,206,respectively, in order of appearance; Table 16, in its entirety,discloses SEQ ID NOS 1,207-1,305, respectively, in order of appearance;Table 17, in its entirety, discloses SEQ ID NOS 1,306-1,404,respectively, in order of appearance; Table 18, in its entirety,discloses SEQ ID NOS 1,405-1,503, respectively, in order of appearance;Table 19, in its entirety, discloses SEQ ID NOS 1,504-1,602,respectively, in order of appearance; Table 20, in its entirety,discloses SEQ ID NOS 1,603-1,701, respectively, in order of appearance;Table 21, in its entirety, discloses SEQ ID NOS 1,702-1,800,respectively, in order of appearance; Table 22, in its entirety,discloses SEQ ID NOS 1,801-1,899, respectively, in order of appearance;Table 23, in its entirety, discloses SEQ ID NOS 1,900-1,998,respectively, in order of appearance; Table 24, in its entirety,discloses SEQ ID NOS 1,999-2,097, respectively, in order of appearance;Table 25, in its entirety, discloses SEQ ID NOS 2,098-2,196,respectively, in order of appearance; Table 26, in its entirety,discloses SEQ ID NOS 2,197-2,295, respectively, in order of appearance;Table 27, in its entirety, discloses SEQ ID NOS 2,296-2,394,respectively, in order of appearance; Table 28, in its entirety,discloses SEQ ID NOS 2,395-2,493, respectively, in order of appearance;Table 29, in its entirety, discloses SEQ ID NOS 2,494-2,592,respectively, in order of appearance; Table 30, in its entirety,discloses SEQ ID NOS 2,593-2,691, respectively, in order of appearance;Table 31, in its entirety, discloses SEQ ID NOS 2,692-2,790,respectively, in order of appearance; Table 32, in its entirety,discloses SEQ ID NOS 2,791-2,889, respectively, in order of appearance;Table 33, in its entirety, discloses SEQ ID NOS 2,890-2,988,respectively, in order of appearance; Table 34, in its entirety,discloses SEQ ID NOS 2,989-3,087, respectively, in order of appearance;Table 35, in its entirety, discloses SEQ ID NOS 3,088-3,186,respectively, in order of appearance). In some embodiments, the epitopelibrary comprises at least 100, at least 200, or at least 300 epitopesfrom the list of epitopes in Tables 2-3 and 5-37 (Table 5, in itsentirety, discloses SEQ ID NOS 118-216, respectively, in order ofappearance; Table 6, in its entirety, discloses SEQ ID NOS 217-315,respectively, in order of appearance; Table 7, in its entirety,discloses SEQ ID NOS 316-414, respectively, in order of appearance;Table 8, in its entirety, discloses SEQ ID NOS 415-513, respectively, inorder of appearance; Table 9, in its entirety, discloses SEQ ID NOS514-612, respectively, in order of appearance; Table 10, in itsentirety, discloses SEQ ID NOS 613-711, respectively, in order ofappearance; Table 11, in its entirety, discloses SEQ ID NOS 712-810,respectively, in order of appearance; Table 12, in its entirety,discloses SEQ ID NOS 811-909, respectively, in order of appearance;Table 13, in its entirety, discloses SEQ ID NOS 910-1,008, respectively,in order of appearance; Table 14, in its entirety, discloses SEQ ID NOS1,009-1,107, respectively, in order of appearance; Table 15, in itsentirety, discloses SEQ ID NOS 1,108-1,206, respectively, in order ofappearance; Table 16, in its entirety, discloses SEQ ID NOS 1,207-1,305,respectively, in order of appearance; Table 17, in its entirety,discloses SEQ ID NOS 1,306-1,404, respectively, in order of appearance;Table 18, in its entirety, discloses SEQ ID NOS 1,405-1,503,respectively, in order of appearance; Table 19, in its entirety,discloses SEQ ID NOS 1,504-1,602, respectively, in order of appearance;Table 20, in its entirety, discloses SEQ ID NOS 1,603-1,701,respectively, in order of appearance; Table 21, in its entirety,discloses SEQ ID NOS 1,702-1,800, respectively, in order of appearance;Table 22, in its entirety, discloses SEQ ID NOS 1,801-1,899,respectively, in order of appearance; Table 23, in its entirety,discloses SEQ ID NOS 1,900-1,998, respectively, in order of appearance;Table 24, in its entirety, discloses SEQ ID NOS 1,999-2,097,respectively, in order of appearance; Table 25, in its entirety,discloses SEQ ID NOS 2,098-2,196, respectively, in order of appearance;Table 26, in its entirety, discloses SEQ ID NOS 2,197-2,295,respectively, in order of appearance; Table 27, in its entirety,discloses SEQ ID NOS 2,296-2,394, respectively, in order of appearance;Table 28, in its entirety, discloses SEQ ID NOS 2,395-2,493,respectively, in order of appearance; Table 29, in its entirety,discloses SEQ ID NOS 2,494-2,592, respectively, in order of appearance;Table 30, in its entirety, discloses SEQ ID NOS 2,593-2,691,respectively, in order of appearance; Table 31, in its entirety,discloses SEQ ID NOS 2,692-2,790, respectively, in order of appearance;Table 32, in its entirety, discloses SEQ ID NOS 2,791-2,889,respectively, in order of appearance; Table 33, in its entirety,discloses SEQ ID NOS 2,890-2,988, respectively, in order of appearance;Table 34, in its entirety, discloses SEQ ID NOS 2,989-3,087,respectively, in order of appearance; Table 35, in its entirety,discloses SEQ ID NOS 3,088-3,186, respectively, in order of appearance).

Computational Methods for Modifying Protein Sequences to Improve theirCrystallization

Methods for modifying protein amino acid sequences to improvecrystallization properties of the protein can be implemented on a server(in some instances referred to herein as the “protein engineering”server). In some embodiments, the server accepts a target proteinsequence from a user and outputs one or more (in some embodimentsseveral) protein sequences related to the target sequence, but havingamino acid mutations that will improve crystallization of the targetsequences. In general, the predicted secondary and tertiary structure ofthe target protein sequence is preserved in the modified protein.

One such embodiment of the method is described with reference to aprotein engineering server described with reference to FIG. 6. In thisembodiment, a user provides the amino acid sequence of the targetprotein to the server (the server receives the target protein sequencefrom the user). The server finds homologous protein sequences, forexample using a program such as BLASTp, available through the NationalCenter for Biotechnology Information (www.ncbi.nlm.nih.gov), and aredescribed in, for example, Altschul et al. (1990), J. Mol. Biol.215:403-410; Gish and States (1993), Nature Genet. 3:266-272; Madden etal. (1996), Meth. Enzymol. 266:131-141; Altschul et al. (1997), NucleicAcids Res. 25:33 89-3402); Zhang et al. (2000), J. Comput. Biol.7(1-2):203-14.

The server then performs a multiple sequence alignment of the targetsequence with the homologous protein sequences for example using aprogram such as CLUSTAL (Chema et al., Multiple sequence alignment withthe Clustal series of programs. Nucleic Acids Res 31(13):3497-500(2003)). The server can also predict the structure of the target proteinsequences, for example using a program such as PHD/PROF (Rost, B., PHD:predicting one-dimensional protein structure by profile-based neuralnetworks. Methods in Enzymology 266, 525-539 (1996)). The epitopeengineering part of the server takes one or more inputs selected fromany combination of the target protein sequence, multiple sequencealignments, predicted secondary structure and the epitope subsequencelibrary and provides a list of recommended mutations to improve proteincrystallization. The output from the server can either be in the form ofa list of mutations to be made in the target sequence or in the form ofone or more amino acid sequences of the modified protein.

In some embodiments, multiple epitope subsequences are introduced in theamino acid sequence of the target protein simultaneously to provide amodified protein. For example, 1, 2, 3, 4, 5, or more epitopesubsequences can be introduced into the same target protein to generatea modified protein.

In some embodiments, the engineering part of the server uses one or moreof the following epitope prioritization criteria: over-representationP-value of the epitope subsequence in packing interfaces; fraction ofoccurrences of that epitope subsequence that make crystal-packingcontacts in the PDB (i.e., that reside within EBIEs); frequency ofoccurrence of that epitope subsequence in the PDB database; sequencediversity of proteins containing that epitope subsequence in the PDB;sequence diversity of partner epitopes interacting with thecorresponding epitope across crystal-packing interfaces in the PDB;absence of non-water bridging ligands in the crystal-packinginteractions made by the corresponding epitopes in the PDB; lack ofincrease in hydrophobicity of the modified protein by introducing theepitope subsequence; or predicted influence of the epitope subsequenceon the solubility of the modified protein. Each of the prioritizationcriteria can be assigned a different weight, including no weight. Anycombination of these prioritization criteria can be used.

In some embodiments, an epitope subsequence that is over-represented byP-value of the epitope subsequence in the epitope subsequence library isa particularly suitable epitope subsequence for improving proteincrystallization.

Fraction of epitope subsequence in crystal-packing contacts is theredundancy-corrected number of an epitope subsequence in crystal-packingcontacts in the PDB divided by the redundancy-corrected total number ofthe epitope subsequence in the PDB. In some embodiments, an epitopesubsequence for which a a high fraction of its occurences in the PDBoccur in crystal-packing contacts is a particularly suitable epitope forimproving protein crystallization.

In some embodiments, an epitope with a high frequency of occurrence inthe PDB is a particularly suitable epitope subsequence for improvingprotein crystallization. In some embodiments, an epitope subsequencethat is present in proteins of diverse sequence in the PDB is aparticularly suitable epitope subsequence for improving proteincrystallization.

Partner epitopes are other epitopes contacted by an epitope in the PDB.In some embodiments, an epitope subsequence whose corresponding epitopescontact a diverse set of different epitopes in the PDB is a particularlysuitable epitope for improving protein crystallization.

Non-water bridging ligands are non-protein molecules such as nucleotidesand buffer salts. In some embodiments, an epitope subsequence whosecorresponding epitopes frequently make contacts to partner epitopes viaa non-water bridging ligand in the PDB is not a particularly suitableepitope subsequence for improving protein crystallization.

In some embodiments, an epitope subsequence that does not increase thehydrophobicity of the modified protein is a particularly suitableepitope subsequence for improving protein crystallization.

In some embodiments, an epitope subsequence that does not reduce thesolubility of the modified protein is a particularly suitable epitopesubsequence for improving protein crystallization. Solubility of aprotein can be predicted, for example, using a computational predictorof protein expression/solubility (PES) was produced (available online athttp://nmr.cabm.rutgers edu:8080/PES/) (Price et al., 2011, MicrobialInformatics and Experimentation, 1:6, doi:10.1186/2042-5783-1-6).Solubility can also be predicted as described in PCT/US11/24251, filedFeb. 9, 2011.

In some embodiments, the prioritized selection criterion isover-representation ratio, using a P-value cutoff. In some embodiments,the selection criteria are selected to prioritize mutations improvingover-representation ratio at a given site (i.e., avoiding removing anepitope subsequence with a better ratio than the new epitopesubsequence). In some embodiments, the selection criteria are selectedto prioritize epitopes subsequence observed in packing interactions inat least 50 sequence-unrelated proteins (“chainsets”) in the PDB. Insome embodiments, the selection criteria are selected to favorsubstitutions maintaining or increasing polarity over those reducingpolarity.

The list of epitopes subsequence in the epitope subsequence library canbe obtained from the comprehensive hierarchical analysis of the entiretyof the PDB (several million epitopes total, the counts for each beingredundancy-corrected), obtained for example as described below, which isthen culled by the over-representation significance P-value against theBonferroni-corrected 95% significance threshold. Epitopes subsequencecan be discarded if they primarily participate only in solventmolecule-mediated bridging interactions involving molecules other thanwater, such as epitopes in nucleotide-binding motifs. Epitopesubsequences can also be discarded if the total number of distinctprotein homology sets that the corresponding epitopes appears in is toolow, to ensure that the epitope's source structures have some variety.

In some embodiments, the resulting epitope subsequence library contains1000-3000 epitopes. In some embodiments, the epitope subsequence librarycontains about 1000, about 2000, or about 3000 epitopes. In a specificembodiment, the epitope subsequence library contains about two-thousandepitopes.

In some embodiments, the epitope subsequences are 1-6 residues in size.In other embodiments, the epitope subsequences are 2-15 residues insize. Each epitope also has a secondary structure mask associated withit, for example, HHH, CCCC, HCCCH, ECCE, where H=helix, C=coli andE=beta strand.

In some embodiments, to generate mutation suggestions to improvecrystallization for a protein of unknown structure, the method combinesthe epitope subsequence library, a secondary structure prediction byPHD/PROF, and a multiple sequence alignment of proteins homologous tothe target. At every position in the target protein sequence, the methodexamines whether any one of the epitope subsequences from the epitopelibrary can be introduced there through a change of a few amino acids.In some embodiments, a mutation at any one position is only allowed ifthe new amino acid can also be found at the same aligned position in oneof the other homologous proteins. In some embodiments, “correlatedevolution” metrics (Liu et al., Analysis of correlated mutations inHIV-1 protease using spectral clustering. Bioinformatics 2008, 24 (10),1243-50; Eyal et al., Rapid assessment of correlated amino acids frompair-to-pair (P2P) substitution matrices. Bioinformatics 2007, 23 (14),1837-9; Hakes et al., Specificity in protein interactions and itsrelationship with sequence diversity and coevolution. Proceedings of theNational Academy of Sciences of the United States of America 2007, 104(19), 7999-8004; Kann et al., Correlated evolution of interactingproteins: looking behind the mirrortree. J Mol Biol 2009, 385 (1), 91-8;Kann et al., Predicting protein domain interactions from coevolution ofconserved regions. Proteins 2007, 67 (4), 811-20) can be used todeprioritize mutations anti-correlated with residue identity at otherpositions in the protein sequence to be mutated, which may be predictiveof reduced stability of modified proteins.

In some embodiments, the secondary structure of the epitope subsequenceto be inserted matches the predicted secondary structure (within sometolerated deviation). These criteria increase the probability that themutations do not destabilize the target protein by introducingbiophysically incongruent changes.

In some embodiments, there are approximately 100-300 epitopesubsequences from the library that can be introduced at some positionwithin the sequence in agreement with these guidelines.

In some embodiments, the epitope subsequences that are expected toimprove crystallization of the target protein are sorted by theirover-representation ratio in the PDB and presented to the researcher.The researcher can choose which and how many mutations to make,preferentially starting from the top of the list, depending on theavailable resources and specific peculiarities of the target protein.

Protein Engineering Server

The techniques, methods and systems disclosed herein may be implementedas a computer program product for use with a computer system orcomputerized electronic device. Such implementations may include aseries of computer instructions, or logic, fixed either on a tangiblemedium, such as a computer readable medium (e.g., a diskette, CD-ROM,ROM, flash memory or other memory or fixed disk) or transmittable to acomputer system or a device, via a modem or other interface device, suchas a communications adapter connected to a network over a medium.

The medium may be either a tangible medium (e.g., optical or analogcommunications lines) or a medium implemented with wireless techniques(e.g., Wi-Fi, cellular, microwave, infrared or other transmissiontechniques). The series of computer instructions embodies at least partof the functionality described herein with respect to the system. Thoseskilled in the art should appreciate that such computer instructions canbe written in a number of programming languages for use with manycomputer architectures or operating systems.

Furthermore, such instructions may be stored in any tangible memorydevice, such as semiconductor, magnetic, optical or other memorydevices, and may be transmitted using any communications technology,such as optical, infrared, microwave, or other transmissiontechnologies.

It is expected that such a computer program product may be distributedas a removable medium with accompanying printed or electronicdocumentation (e.g., shrink wrapped software), preloaded with a computersystem (e.g., on system ROM or fixed disk), or distributed from a serveror electronic bulletin board over the network (e.g., the Internet orWorld Wide Web). Of course, some embodiments of the invention may beimplemented as a combination of both software (e.g., a computer programproduct) and hardware. Still other embodiments of the invention areimplemented as entirely hardware, or entirely software (e.g., a computerprogram product).

Efficient Mutational Engineering of Protein Crystallization

The invention provides a new approach to engineering improved proteincrystallization based on introduction of historically successfulcrystallization epitopes into crystallization-resistant proteins.Datamining the results of high-throughput experimental studies indicatedthat crystallization propensity is controlled primarily by theprevalence of low-entropy surface epitopes capable of mediatinghigh-quality crystal-packing interactions (Price et al., Understandingthe physical properties that control protein crystallization by analysisof large-scale experimental data. Nat Biotechnol 27 (1), 51-7 (2009)).The PDB contains a massive archive of such epitopes in deposited crystalstructures.

In one embodiment, the invention provides methods for mutationalengineering of crystallization that are efficient enough to enable thestructure of any target protein to be determined with relatively modesteffort compared to pre-existing methods.

The thermodynamics of crystallization have been analyzed extensively. Ifthe individual packing interfaces in the lattice have favorable freeenergy, formation of a regular lattice is thermodynamically favoredbecause of the consistent gain in energy for every added molecule. Theprevalence of surface epitopes with high propensity to form suchfavorable interactions is likely to determine whether a particularprotein can find a regular lattice structure with favorableintermolecular interactions or whether it precipitates amorphously withheterogeneous packing interactions. Increasing the prevalence of surfaceepitopes with favorable packing potential, as evidenced by participationin many interfaces in the PDB, can increase the probability of highquality crystallization.

Surface Entropy is a Determinant of Protein Crystallization Propensity

Results of large-scale experimental studies were analyzed to developinsight into the physical properties controlling proteincrystallization. Statistical analyses were used to evaluate therelationship between protein sequence and successful crystal-structuredetermination (Price et al., Understanding the physical properties thatcontrol protein crystallization by analysis of large-scale experimentaldata. Nat Biotechnol 27 (1), 51-7 (2009)). The dataset comprised 679biochemically well-behaved proteins that were taken through a consistentexpression, purification, quality-control, and crystallization pipelineto yield 157 structures. Proteins yielding crystals of insufficientquality for structure determination were considered failures even ifdiffraction was observed, as occurred for 39 proteins. Retrospectiveanalyses demonstrated that some key sequence features of these are moresimilar to proteins that failed to yield structures than those that did.Sequence properties that were analyzed included the frequency of eachamino acid, mean hydrophobicity, mean side-chain entropy, a variety ofelectrostatic parameters, and the fraction of residues predicted to bedisordered by the program DISOPRED2 (Ward et al., The DISOPRED serverfor the prediction of protein disorder. Bioinformatics 20 (13), 2138-9(2004)). Logistic regressions were performed to evaluate therelationship between each of these continuous sequence parameters andthe binary outcome of the crystallization/structure-determinationeffort. These analyses demonstrated that many sequence parameters aresignificantly predictive of outcome. However, multiple logisticregression and other analyses showed that most sequence effects aresurrogates for side-chain entropy. Statistically independentcontributions are made only by the predicted fraction of disorderedresidues (an inhibitory factor) and the fractional content of Ala, Gly,and possibly Phe residues (all positively correlated with success).Furthermore, we demonstrated that the side-chain entropy effect islocalized to residues predicted to be surface exposed according to thePHD-PROF program (Rost, B., PHD: predicting one-dimensional proteinstructure by profile-based neural networks. Methods in Enzymology 266,525-539 (1996)), which predicts both secondary structure and surfacelocalization with ˜80% accuracy.

These analyses establish surface entropy as a major determinant ofprotein crystallization propensity. They also indicated that the Glyresidues promoting successful crystallization are localized to shortsurface loops and likely to be at least partially buried ininter-protein packing interfaces.

Thermodynamic Stability is not a Major Determinant of ProteinCrystallization Propensity

In the studies described herein, thermodynamic stabilities of asubstantial subset of proteins in the crystallization dataset weremeasured. These studies showed a small advantage for hyper-stableproteins but equivalent crystallization propensity for proteins spanningthe wide range of stability characteristic of the most proteins frommesophilic organisms. Therefore, thermodynamic stability is not a majordeterminant of protein crystallization. In aggregate, large-scaleexperimental studies support the premise that protein surfaceproperties, especially the prevalence of well-ordered epitopes capableof mediating inter-protein packing interactions, are paramount indetermining crystallization propensity. This basis provided the impetusto systematically characterize such epitopes in the existing PDB withthe goal of developing methods to use historically successful epitopesfor rational engineering of improved protein crystallization.

Hydrodynamic Heterogeneity and Aggregation Impede Crystallization

The final crystallization stock of every protein in the experimentaldataset was characterized using gel-filtration/static-light-scatteringanalyses. Consistent with previous theoretical and protein-engineeringstudies, stable oligomers crystallize significantly better thanmonomers. However, hydrodynamic heterogeneity impedes crystallizationand aggregation strongly inhibits it. Although formation of specificoligomers strongly promotes crystallization, heterogeneousself-association inhibits it. Successful crystallization thus requiresminimal non-specific self-association in dilute aqueous buffers butstrong self-association under the low water-activity conditions used toform protein crystals. Accordingly, proteins with crystal structuresdeposited in the PDB should be enriched for surface epitopes with thisspecial combination of physical properties.

Single Amino-Acid Properties that Promote Crystallization Reduce ProteinSolubility

In a follow-up study, equivalent datamining methods were used to analyzecorrelations between sequence properties and in vivoexpression/solubility results (Price et al., 2011, Microbial Informaticsand Experimentation, 1:6, doi:10.1186/2042-5783-1-6). This studyexamined 7733 proteins expressed and purified consistently using a T7vector in codon-enhanced E. coli BL21λ(DE3) cells (PCT/US11/24251, filedFeb. 9, 2011). The relationship between primary sequence properties andthe probability of obtaining a protein preparation useful for structuralstudies were analyzed. A computational predictor of proteinexpression/solubility (P_(ES)) was produced (available online athttp://nmr.cabm.rutgers.edu:8080/PES/). With the exception of predictedbackbone disorder, which inhibits both crystallization and solubility,every sequence property that promotes crystallization reduces solubilityand vice-versa. These results demonstrate that single-residue mutationsdesigned to enhance crystallization will tend to reduce the probabilityof obtaining a soluble protein preparation suitable for crystallizationscreening (FIG. 7).

Moreover, published results showed that hydrodynamic heterogeneity andaggregation, which are correlated with low solubility, significantlyimpede crystallization (Price et al., Understanding the physicalproperties that control protein crystallization by analysis oflarge-scale experimental data. Nat Biotechnol 27 (1), 51-7 (2009);Ferre-D'Amare and Burley, Use of dynamic light scattering to assesscrystallizability of macromolecules and macromolecular assemblies.Structure, 2 (5), 357-9 (1994)). Therefore, any strategy focused onsingle-residue substitutions will suffer from problems with proteinsolubility, as observed for the Surface Entropy Reduction method.

Observations on the statistical influence of individual amino acidssuggest that more complex sequence epitopes are needed to provide thesimultaneous combination of good solubility and low surface entropycharacteristic of proteins yielding crystal structures. Theseobservations support the strategy of mining such epitopes out ofexisting crystal structures in the PDB.

Identification and Analysis of Epitopes Mediating Inter-Protein PackingInteractions in the PDB

A hierarchical analytical scheme was developed to identify contiguousepitopes potentially useful for protein engineering and was used toanalyze all inter-protein crystal-packing interactions in the PDB (FIG.3). Bold lines represent protein chains, grey lines inter-atomiccontacts ≤4 Å, and numbered circles show representative elements.

FIG. 5 shows selected statistics from application of our analyticalscheme to all crystal structures in the PDB that do not have excessivelyclose inter-protein contacts (39,208 entries). FIG. 5A shows histogramsshowing distributions of the fraction of residues participating ininter-protein packing contacts. FIG. 5B shows histograms showing numberof interfaces per crystal. FIG. 5C is a cumulative distribution graphshowing fraction of interfaces equal to or smaller in size than thenumber indicated on the abscissa. In this graph, residues from the twointeracting molecules are counted separately. The curve labeled“Largest” shows data for the single largest non-proper interface in eachcrystal. FIG. 5D shows cumulative size and range distributions forhierarchically defined packing elements (counting residues from one ofthe interacting molecules).

The average numbers of total, proper, and non-proper interfaces perprotein molecule are 6.9, 1.8 and 5.1, respectively (FIG. 5A). While atleast four interfaces are required for a molecule to form a3-dimensional lattice, fewer are possible if multiple molecules arepresent in the asymmetric unit. Proteins generally contain only a smallnumber of interfaces above the minimum required for lattice formation,indicating that most interfaces contribute to structural stabilizationof the lattice. On average, 50% of surface-exposed residues and 36% ofall residues participate in inter-protein packing interactions (FIG.5B). While interfaces range widely in size, 36% of all interfaces and42% of non-proper interfaces contain 10 or fewer residues, countingcontributions from both sides of the interface (˜5 from eachparticipating molecule) (FIG. 5C). The small size of the averageinterface is encouraging relative to the feasibility of engineeringinterface formation. FIG. 5D shows the cumulative size/rangedistributions for all EBIEs, CBIEs, and half-interfaces (i.e.,participating residues from one of the two interacting molecules). Thesedata show that, even though some interfaces are complex, most aretopologically simple and local in primary sequence. Half of allhalf-interfaces are under eight residues in size, and a quarter (8678total) are under eight residues in range (separation) in the polypeptidechain. FBIEs contain on average fewer than two EBIEs (not shown), andmost EBIEs are less than 4 residues in size and 10 in range. These smallEBIEs represent prime candidates for engineering improvedcrystallization.

Quantifying Similarity in the Crystal-Packing Interactions of HomologousProteins Demonstrates Pervasive Polymorphism in Inter-Protein Interfaces

A general method has been developed to quantify the similarity betweendifferent inter-protein packing interfaces formed by homologousproteins. Its foundation is a B-factor-weighted count (C_(ij)) ofinter-atomic contacts between residues i and j across the interface:

$C_{ij} = {\sum\limits_{{atom}.{pairs}}\;( \frac{\langle B \rangle_{2 - {10\%}}}{\sqrt{B_{m}B_{n}}} )^{n}}$

The terms B_(m) and B_(n) are the atomic B-factors of the contactingatoms in residues i and j, respectively (i.e., atoms with centersseparated by less than 4 Å), while <B>_(2-10%) represents an estimate ofthe B-factor of the most ordered atoms in the structure (which iscalculated as the average B-factor of atoms in the 2^(nd) through10^(th) percentiles). An upper limit of 1.0 is imposed on the B-factorratio (i.e., it is set to 1.0 whenever (B_(m)B_(n))^(1/2)<<B>_(2-10%)).The exponent n is an adjustable parameter in our software that allowsanalyses to be performed either without (n=0) or with (n≥1)down-weighting of contacts between atoms with high B-factors. Suchatoms, which have enhanced disorder, may contribute less to interfacestabilization, but prior literature on this topic is lacking. Therefore,an analytical approach has been developed facilitating exploration ofB-factor effects. Specifically, using higher values of n in our scoringfunction progressively down-weights high B-factor contacts.

Identification of Statistically Over-Represented Epitope Subsequences inCrystal-Packing Interfaces in the PDB Leads to Novel Ideas forEngineering Improved Protein Crystallization

To identify promising motifs for use in enhancing crystallizationpropensity, statistical analyses of sequence patterns occurring inprotein segments with specific secondary structures were conducted, asanalyzed using the DSSP algorithm (Kabsch and Sander, Dictionary ofprotein secondary structure: pattern recognition of hydrogen-bonded andgeometrical features. Biopolymers 22 (12), 2577-637 (1983)), which makesthree-state assignments of α-helix (H), β-strand (E), or loop or coil(C).

The primary reason for using a simultaneous sequence/secondary-structuredefinition of a packing epitope is to facilitate application of thesedata to epitope-engineering. A given amino acid sequence will generallyhave different conformations at different sites in a protein. However,local conformation is likely to be similar when the sequence occurs inthe same secondary structure (i.e., on the surface of a β-strand or inan α-helix capping motif). An epitope-visualization tool, implemented aspart of our epitope-engineering web-server described below, enablesusers to verify this assumption for specific epitopes and providessupport for its general validity.

Previously, sophisticated primary-sequence-analysis algorithms have beendeveloped to predict local protein secondary structure as well assurface-exposure even in the absence of the 3-dimensional structure ofthe protein. PHD-PROF is one such program that was trained using DSSP,the software used to classify all crystal-packing epitopes in the PDB.Productive use was made of PHD-PROF in our publishedcrystallization-datamining studies described above. PHD-PROF has beencross-validated and achieves ˜80% accuracy in identifying residuesecondary structure and surface-exposure status based on primarysequence alone. These results support the likely efficacy of usingPHD-PROF to predict local secondary structure to guide introduction ofhistorically successful crystallization epitopes at productive sites inproteins with unknown tertiary structure.

The initial approach to prioritizing the most promising crystallizationepitope subsequences for engineering applications involves ranking theirdegree of over-representation in packing contacts in non-BioMTinterfaces in the PDB (FIG. 1). Accurate assessment ofover-representation requires careful correction for redundancy inprevious observations of crystal-packing as well as normalization forthe biased distribution of amino acids found on protein surfaces. PSS,described above, is used to quantitatively correct epitope subsequencecounts for redundancies between the different packing interfaces inwhich they are found. The marginal count for each occurrence of asub-epitope in an interface in a crystal is inversely proportional tothe total number of crystals mostly identical to the given crystal, andto the number of interfaces within the crystal mostly identical to thegiven interface. Epitope subsequences in bio-oligomer (BIOMT) interfacesdo not contribute to the count. This approach substantially boostssignal strength by counting the multiple contacts formed by anefficacious epitope subsequence found in crystal structures ofhomologous proteins when that epitope subsequence repeatedlyparticipates in novel packing interactions.

To calculate the whether a given epitope subsequence appears in crystalpacking interfaces more frequently than expected by chance, each epitopesubsequences' count must be calibrated against the total number ofoccurrences of that subsequence in the sequence space of the PDB, andagainst the variable probability of finding any given amino acid oramino acid sequence on the protein's surface rather than in theinterior. For an epitope subsequence with interaction mask m (such as XXor XxxxX), primary and secondary sequence i (such as “ExxxR HhhhH”(“ExxxR” disclosed as SEQ ID NO: 50)) and surface exposure profile s(such as SIIIS), its redundancy-weighted count in crystal packinginterfaces is e_msi (the “epitope subsequence” count) and itsredundancy-weighted count in the sequence space is p_msi (the “prior”count). The surface profile is calculated by DSSP, which uses aquantitative cut-off for designation of interior residues, allowing upto 15% of their surface area to be solvent exposed. Because of thisuncertainty, about 10% of all residues participating in packing contactsare designated as interior. Since the surface profile designations arevariable and to some degree arbitrary, they need to be abstracted awayusing the “surface-expected” method, which predicts how frequently aepitope subsequence would participate in crystal packing interactions ifthe surface profile bias was removed. The total number of occurrences ofa epitope subsequence with interaction mask m and sequence i ininteractions is the sum of the counts across all possible surfaceprofiles:e_mi=Σ_se_msi

While the prior count of a epitope subsequence with mask m and sequencei is accordingly:p_mi=Σ_sp_msi

The expected number of occurrences of the given epitope subsequence ininteractions depends on the frequency of occurrences of all epitopesubsequences with the same interaction mask and surface profile, summedacross all possible surface profiles:E(e_mi)=Σ_i[(Σ_je_msj)/(Σ_jp_msj)*p_msi]

Finally, the probability that the calculated epitope subsequence countcould have been observed by chance can be calculated by integrating theupper tail of the binomial distribution B(n, p, k) where:k_mi=e_mi,n_mi=p_mi, andp_mi=E(e_mi)/p_mi.

If the calculated probability is below the Bonferonni-correctedsignificance level of 5%, the given epitope subsequence is designated tobe “over-represented”, and its over-representation ratio is equal to:e_mi/E(e_mi).

The initial analysis conducted using these methods evaluated allpossible secondary-structure-specific epitopes subsequences in proteinsegments from two to six residues in length. The interacting residues inthe epitope subsequence had to occur in a single EBIE, while both theinteracting and non-interacting residues had to match thesecondary-structure pattern at every position. This analysis covers 31different interaction masks giving a total of over 57 billion possiblesecondary-structure-specific sub-epitopes. However, only 54,317,358 ofthese actually occur in crystal structures in the PDB, so this numberwas used as the correction factor for multiple-hypothesis testing. Afterapplying this correction, 2,040 of these secondary-structure-specificepitope subsequences are over-represented at a Bonferroni-corrected 5%significance level of 9.2×10⁻¹⁰, while also meeting a small set ofadditional selection criteria (at least 10 redundancy-corrected countsin epitopes, no more than 50% of occurrences involving non-waterbridging solvent species, and at least a 1.5 ratio ofredundancy-corrected observed vs. expected counts in epitopes).

Table 37 shows the eight top-ranked secondary-structure-specific epitopesubsequences in two classes of interest, continuous dimers (XX mask) anddimers separated by four residues (XxxxX mask).

TABLE 37^(a) (SEQ ID NOS 42-57, respectively, in order of appearance)Redundancy- Non- Over- % identity in Secondary corrected homologousrepresentation Fraction in Fraction non- partner Sequence structurecounts chains P-value ratio epitopes H₂O solvent epitopes LP CC 36452421 5.0e−79 1.3 0.18 0.18 12% GY CC 1961 1241 1.6e−67 1.4 0.22 0.24 12%PN CC 2685 1612 3.9e−62 1.3 0.27 0.19 13% GK CH 497 277 1.7e−61 2.0 0.240.74 12% DG CC 5443 2805 7.2e−58 1.2 0.25 0.16 13% PG CC 5008 26001.3e−57 1.2 0.25 0.17 12% GF CC 1763 1216 1.0e−55 1.4 0.19 0.21 12% NGCC 4062 2226 2.7e−54 1.2 0.25 0.18 12% ExxxR HhhhH 3547 2041 0.0 2.10.28 0.18 15% RxxxE HhhhH 2928 2328 0.0 2.2 0.26 0.17 15% QxxxD HhhhH1522 1141 1.3e−272 2.3 0.27 0.13 13% RxxxR HhhhH 1627 1078 1.1e−271 2.20.28 0.23 15% ExxxE HhhhH 2968 1998 1.6e−251 1.8 0.23 0.16 15% DxxxRHhhhH 1593 1128 4.1e−246 2.2 0.26 0.17 14% ExxxQ HhhhH 1904 13953.0e−228 2.0 0.24 0.16 14% AxxxR HhhhH 1717 1299 3.6e−186 1.9 0.17 0.1914% ^(a)“Sequence” is the string of amino acid letter codes, withcapital letters indicating amino acid participating in interactions, andlower-case x's indicating intervening residues (which may or may not beinteracting as well). “Secondary structure” indicates structure lettercodes (H = helix, E = sheet, C = coil). “Redundancy-corrected counts” iscalculated as described in above. “Non-homologous chains” is the numberof chain homology sets in which the epitope can be found in interactions(a chain homology set contains all protein chains that have greater than25% sequence identity). “P-value” and “over-representation ratio” arecalculated as described above. “Fraction in epitopes” is the ratio ofthe observed redundancy-weighted surface-profile-summed epitope count tothe observed prior count. “Fraction non-water solvent” is the fractionof the total redundancy-weighted number of occurrences of the epitopethat participate in inter-protein interactions bridged by a solventmolecule other than water, such as salt ions or nucleotides (ATP). “% idpartner epitopes” is the average sequence identity of the partnerepitopes of this epitope - the strings of amino acid letter codescorresponding to the residues of the protein with which the residues ofthe given epitope interact in every interface in which the epitopeappears.

Evaluation of these classes is informative for several reasons,including the fact their P-values can be compared directly because theyhave an equivalent number of occurrences in the PDB. The mostover-represented epitope subsequences in the two classes containdifferent residues, indicating that our statistical methods give resultssensitive to local stereochemistry and not merely the amino acidcomposition. The top-ranking continuous dimers are enriched in Glyresidues in loops, consistent with prediction from our earliercrystallization datamining studies that such residues are enriched inpacking interfaces (Price et al., Understanding the physical propertiesthat control protein crystallization by analysis of large-scaleexperimental data. Nat Biotechnol 27 (1), 51-7 (2009)).

Remarkably, dimers separated by four residues are enriched inhigh-entropy, charged amino acids located on the surfaces of α-helicesor in their capping motifs. Given these relative locations, thehigh-entropy side-chains are likely to be entropically restricted bymutual salt-bridging or hydrogen-bonding (H-bonding) interactions withinthe secondary-structure specific epitope subsequence. Immobilization ofthese high-entropy side-chains by local tertiary interactions in thenative structure of a protein enables them to participate incrystal-packing interactions without incurring the entropic penaltyassociated with their immobilization from a disordered conformation onthe surface of the protein.

Simple Local Structural Motifs Represent Highly Promising Candidates forEngineering Improved Protein Crystallization Behavior Based on NovelAmino-Acid Substitutions

Certain local structural motifs are highly polar and therefore much lesslikely than hydrophobic substitutions to reduce protein solubility,which is a major problem with the Surface Entropy Reduction method(Cooper et al., Protein crystallization by surface entropy reduction:optimization of the SER strategy. Acta crystallographica, 63 (Pt 5),636-45 (2007); Derewenda and Vekilov, Entropy and surface engineering inprotein crystallization. Acta crystallographica 62 (Pt 1), 116-24(2006); Longenecker et al., Protein crystallization by rationalmutagenesis of surface residues: Lys to Ala mutations promotecrystallization of RhoGDI. Acta crystallographica, 57 (Pt 5), 679-88(2001)). Second, they occur in secondary-structure motifs that arereliably classified by standard prediction algorithms, both in terms oftheir location and their solvent exposure status. Therefore,epitope-engineering efforts should be able to efficiently target themost promising regions of the subject protein, even when its tertiarystructure is unknown. Third, it is reassuring that the sub-epitopes inboth classes in Table 37 interact with partner epitopes with highlydiverse sequences, consistent with our goal of engineering the surfaceof a protein to have higher interaction probability (i.e., rather thanattempting to engineer specific pair-wise packing interactions). Table38 only shows a small fraction of the statistically over-representedsecondary-structure-specific sub-epitopes in the PDB. The full set inTable 37 (Appendix A) covers a much wider variety of sequences andsecondary structures, although many of them echo similar physiochemicalthemes.

Epitope-Engineering Software

Software was written to determine all possible ways that thestatistically over-represented epitope subsequences described above canbe introduced into a target protein consistent with the sequence profileof the corresponding functional family (FIG. 1). The program takes twoinput files, one a FASTA-formatted file with a set of homologous proteinsequences (with the target protein at the top) and the other thesecondary-structure prediction output from PHD/PROF. After usingClustalW to align the homologs, the software systematically analyzes thelocations where any of the sub-epitopes can be engineered into thetarget protein consistent with two criteria.

First, based on the PHD/PROF prediction, the secondary structure at thesite of mutagenesis must be likely to match that of the sub-epitope.This restriction increases the probability that the engineeredsub-epitope will have a local tertiary structure similar to theover-represented sub-epitopes in the PDB.

Second, in one embodiment, the engineered epitope subsequence containsexclusively amino acids observed to occur at the equivalent position inone of the homologs. In another embodiment, the engineered epitopesubsequence is filtered to not contain residues anti-correlated inhomologs with other amino acids in the target sequence, as determinedusing the “correlated evolution” metrics described above. Restrictingepitope mutations to substitutions observed in a homolog should reducethe chance that the mutations will impair protein stability. In yetanother embodiment, the engineered epitope subsequence is not restrictedat all based on homolog sequence, and a greater risk of proteindestabilization is tolerated. The computer program returns acomma-separated-value file containing a list of candidateepitope-engineering mutations along with statistics characterizing eachepitope subsequence. While this list is sorted according toover-representation P-value, it is readily resorted according to usercriteria in any standard spreadsheet program. For a target protein ˜200residues in length with ˜20 homologous sequences, the program typicallyreturns several hundred candidate mutations. However, longer proteins orproteins with more homologs can yield lists containing thousands ofcandidate mutations.

Methods for Protein Expression

Strategies and techniques for expressing a protein of interest or amodified protein, for producing nucleic acids encoding a protein ofinterest or a modified protein are well-known in the art and can befound, e.g., in Berger and Kimmel, Guide to Molecular CloningTechniques, Methods In Enzymology Vol. 152 Academic Press, Inc., SanDiego, Calif. and in Sambrook et al., Molecular Cloning-A LaboratoryManual (2nd ed.) Vol. 1-3 (1989) and in Current Protocols In MolecularBiology, Ausubel, F. M., et al., eds., Greene Publishing Associates,Inc. and John Wiley & Sons, Inc., (1996 Supplement).

Expression systems suitable for use with the methods described hereininclude, but are not limited to in vitro expression systems and in vivoexpression systems. Exemplary in vitro expression systems include, butare not limited to, cell-free transcription/translation systems (e.g.,ribosome based protein expression systems). Several such systems areknown in the art (see, for example, Tymms (1995) In vitro Transcriptionand Translation Protocols Methods in Molecular Biology Volume 37,Garland Publishing, NY).

Exemplary in vivo expression systems include, but are not limited toprokaryotic expression systems such as bacteria (e.g., E. coli and B.subtilis), and eukaryotic expression systems including yeast expressionsystems (e.g., Saccharomyces cerevisiae), worm expression systems (e.g.Caenorhabditis elegans), insect expression systems (e.g. Sf9 cells),plant expression systems, amphibian expression systems (e.g. melanophorecells), vertebrate including human tissue culture cells, and geneticallyengineered or virally infected whole animals.

Methods Fore Determining Solubility of a Protein

Methods for determining the solubility of a protein are known in theart. For example, a recombinant protein can be isolated from a host cellby expressing the recombinant protein in the cell and releasing thepolypeptide from within the cell by any method known in the art,including, but not limited to lysis by homogenization, sonication,French press, microfluidizer, or the like, or by using chemical methodssuch as treatment of the cells with EDTA and a detergent (see Falconeret al., Biotechnol. Bioengin. 53:453-458 [1997]). Bacterial cell lysiscan also be obtained with the use of bacteriophage polypeptides havinglytic activity (Crabtree and Cronan, J. E., J. Bact., 1984,158:354-356).

Soluble materials can be separated form insoluble materials bycentrifugation of cell lysates (e.g. 18,000×G for about 20 minutes).After separation of lysed materials into soluble and insolublefractions, soluble protein can be visualized by using denaturing gelelectrophoresis. For example, equivalent amount of the soluble andinsoluble fractions can be migrated through the gel. Proteins in bothfractions can then be detected by any method known in the art,including, but not limited to staining or by Western blotting using anantibody or any reagent that recognizes the recombinant protein.

Protein Purification

Proteins can also be isolated from cellular lysates (e.g. prokaryoticcell lysates or eukaryotic cell lysates) by using any standard techniqueknown in the art. For example, recombinant polypeptides can beengineered to comprise an epitope tag such as a Hexahistidine(“hexaHis”) tag (SEQ ID NO: 5,227) or other small peptide tag such asmyc or FLAG. Purification can be achieved by immunoprecipitation usingantibodies specific to the recombinant peptide (or any epitope tagcomprised in the amino sequence of the recombinant polypeptide) or byrunning the lysate solution through an affinity column that comprises amatrix for the polypeptide or for any epitope tag comprised in therecombinant protein (see for example, Ausubel et al., eds., CurrentProtocols in Molecular Biology, Section 10.11.8, John Wiley & Sons, NewYork [1993]).

Other methods for purifying a recombinant protein include, but are notlimited to ion exchange chromatography, hydroxylapatite chromatography,hydrophobic interaction chromatography, preparative isoelectric focusingchromatography, molecular sieve chromatography, HPLC, native gelelectrophoresis in combination with gel elution, affinitychromatography, and preparative isoelectric. See, for example, Marstonet al. (Meth. Enz., 182:264-275 [1990]).

Screening of Modified Proteins for Crystallization

Initial high-throughput crystallization screening can be conducted usingmethods known in the art, for example manually or using the 1,536-wellmicrobatch robotic screen at the Hauptmann-Woodward Institute (Cumbaa etal., Automatic classification of sub-microliter protein-crystallizationtrials in 1536-well plates. Acta Crystallogr. 59, 1619-1627 (2003)).Proteins failing to yield rapidly progressing crystal leads can besubjected to vapor diffusion screening, typically 300-500 conditions(e.g., Crystal Screens I & II, PEG-Ion and Index screens from HamptonResearch or equivalent screens from Qiagen) at either 4° C., 20° C. orboth. Screening can be conducted in the presence of substrate or productcompounds If commercially available. Screening can also be conductedusing the target protein as a control to evaluate the effect of theintroduction of an epitope or multiple epitopes on the crystallizationproperties of the target protein.

All patents, patent applications and publications cited herein arehereby incorporated by reference in their entirety. The disclosures ofthese publications in their entireties are hereby incorporated byreference into this application in order to more fully describe thestate of the art as known to those skilled therein as of the date of theinvention described herein.

The following examples illustrate the present invention, and are setforth to aid in the understanding of the invention, and should not beconstrued to limit in any way the scope of the invention as defined inthe claims which follow thereafter.

EXAMPLES

This invention is further illustrated by the following examples, whichshould not be construed as limiting. Those skilled in the art willrecognize, or be able to ascertain, using no more than routineexperimentation, numerous equivalents to the specific substances andprocedures described herein. Such equivalents are intended to beencompassed in the scope of the claims that follow the examples below.

Example 1—Introduction of Residues from an Observed Crystal-PackingEpitope Improves Crystallization of an Integral Membrane Protein

FIG. 8 shows representative results from an initial attempt to employ apreviously observed crystallization epitope to improve thecrystallization of a difficult protein.

FIG. 8A is a schematic summary of the results from a representativeinitial crystallization screen at 20° C. The MD-to-AG mutant yielded 5excellent hits and 23 total hits, compared to 1 and 8, respectively, forthe wild-type protein. FIG. 8B is a micrograph of one well of excellentlead crystals obtained for the MD-to-AG mutant protein (described below)in this screen. FIG. 8C is the same well from a wild-type screenconducted in parallel.

The subject of this study was a polytopic integral membrane protein fromE. coli called B0914 whose wild-type sequence only yields poor crystals.Manual inspection of a crystal structure of a remote homologue (Dawsonand Locher, Structure of a bacterial multidrug ABC transporter. Nature443 (7108), 180-5 (2006)) revealed that an Ala-Gly (AG) dipeptide in aperiplasmic loop formed part of a crystal-packing interaction. Becausethe frequency of these two residues correlates most strongly withsuccessful crystal structure determination in our published dataminingstudies, it was hypothesized that this dipeptide could be used toengineer improved crystallization of another protein. This sub-epitoperanks 20^(th) among the 400 possibilities in the analysis ofover-represented continuous dimers.

The sub-epitope was introduced into one of the periplasmic loops inprotein B0914, at a site with the sequence met-asp (MD) but where thesequence AG is found in a homolog. This MD-to-AG mutant protein yieldsmore hits and more high quality hits in initial crystallization screens(FIG. 8). Importantly, improved crystallization is obtained even thoughthe interaction partner of the AG epitope from the existing structurewas not introduced into the target protein. A second mutant proteincontaining a similarly chosen crystallization epitope that was notobserved in a homologous protein failed to produce properly foldedprotein, while a series of single-residue substitutions chosen based ondifferent criteria yielded inferior results, including severalsubstitutions recommended by the standard Surface Entropy Reductionalgorithm.

Example 2—Generation of Modified Proteins with Epitopes that IncreaseProtein Crystallization

Amino acid sequences of 13 genes were provided to the server. The aminoacid sequences were:

BhR182-21.1 (SEQ ID NO: 1)MIIREATVQDYEEVARLHTQVHEAHVKERGDIFRSNEPTLNPSFFQAAVQGEKSTVLVFVDEREKIGAYSVIHLVQTPLLPTMQQRKTVYISDLCVDETRRGGGIGRLIFEAIISYGKAHQVDAIELDVYDFNDRAKAFYHSLGMRCQKQTMELPLLEHHHHHH ChR11B-227-489-21.2(SEQ ID NO: 2)NDDVEFRYADFLFKNNNYAEAIEVFNKLEAKKYNSPYIYNRRAVCYYELAKYDLAQKDIETYFSKVNATKAKSADFEYYGKILMKKGQDSLAIQQYQAAVDRDTTRLDMYGQIGSYFYNKGNFPLAIQYMSKQIRPTTTDPKVFYELGQAYYYNKEYVKADSSFVKVLELKPNIYIGYLWRARANAAQDPDTKQGLAKPYYEKLIEVCAPGGAKYKDELIEANEYIAYYYTINRDKVKADAAWKNILALDPTNKKAIDGLKMKLEHHHHHH CvR75A-1-152-21.17 (SEQ ID NO: 3)MKKVYIKTFGCQMNEYDSDKMADVLGSAEGMVKTDNPEEADVILFNTCSVREKAQEKVFSDLGRIRPLKEANPDLIIGVGGCVASQEGDAIVKRAPFVDVVFGPQTLHRLPDLIESRKQSGRSQVDISFPEIEKFDHIPPAKVDGGAAFVSILEHHHHHH EcoxPrrC (SEQ ID NO: 4)MGKTLSEIAQQLSTPQKVKKTVHKEVEATRAVPKVQLIYAFNGTGKTRLSRDFKQLLESKVHDGEGEDEAEQSALSRKKILYYNAFTEDLFYWDNDLQEDAEPKLKVQPNSYTNWLLTLLKDLGQDSNIVRYFQRYANDKLTPHFNPDFTEITFSMERGNDERSAHIKLSKGEESNFIWSVFYTLLDQVVTILNVADPDARETHAFDQLKYVFIDDPVSSLDDNHLIELAVNLAGLIKSSESDLKFIITTHSPIFYNVLFNELNGKVCYMLESFEDGTFALTEKYGDSNKSFSYHLHLKQTIEQAIADNNVERYHFTLLRNLYEKTASFLGYPKWSELLPDDKQLYLSRIINFTSaSTLSNEAVAEPTPAEKATVKLLLDHLKNNCGFWQQEQKNG ER247A-21.2 (SEQ ID NO: 5)MNETAVYGSDENIIFMRYVEKLHLDKYSVKNTVKTETMAIQLAEIYVRYRYGERIAEEEKPYLITELPDSWVVEGAKLPYEVAGGVFIIEINKKNGCVLNFLHSKLEHHHHHH ER40-21-mgk(SEQ ID NO: 6)MSDDNSHSSDTISNKKGFFSLLLSQLFHGEPKNRDELLALIRDSGQNDLIDEDTRDMLEGVMDIADQRVRDIMIPRSQMITLKRNQTLDECLDVIIESAHSRFPVISEDKDHIEGILMAKDLLPFMRSDAEAFSMDKVLRQAVVVPESKRVDRMLKEFRSQRYHMAIVIDEFGGVSGLVTIEDILELIVGEIEDEYDEEDDIDFRQLSRHTWTVRALASIEDFNEAFGTHFSDEEVDTIGGLVMQAFGHLPARGETIDIDGYQFKVAMADSRRIIQVHVKIPDDSPQPKLDELEHHHHHH EwR161-21.1(SEQ ID NO: 7)MQSFDVVIAGGGMVGLALACGLQGSGLRIAVLEKQAAEPQTLGKGHALRVSAINAASECLLRHIGVWENLVAQRVSPYNDMQVWDKDSFGKISFSGEEFGFSHLGHIIENPVIQQVLWQRASQLSDITLLSPTSLKQVAWGENEAFITLQDDSMLTARLVVGADGAHSWLRQHADIPLTFWDYGHHALVANIRTEHPHQSVARQAFHGDGILAFLPLDDPHLCSIVWSLSPEQALVMQSLPVEEFNRQVAMAFDMRLGLCELESERQTFPLMGRYARSFAAHRLVLVGDAAHTIHPLAGQGVNLGFMDVAELIAELKRLQTQGKDIGQHLYLRRYERRRKHSAAVMLASMQGFRELFDGDNPAKKLLRDVGLVLADKLPGIKPTLVRQAMGLHDLPDWLSAGKLEHHHHHH HR4403-86-543-14.1(SEQ ID NO: 8)MGHHHHHHSHMNRFEEAKRTYEEGLKHEANNPQLKEGLQNMEARLAERKFMNPFNMPNLYQKLESDPRTRTLLSDPTYRELIEQLRNKPSDLGTKLQDPRIMTTLSVLLGVDLGSMDEEEEIATPPPPPPPKKETKPEPMEEDLPENKKQALKEKELGNDAYKKKDFDTALKHYDKAKELDPTNMTYITNQAAVYFEKGDYNKCRELCEKAIEVGRENREDYRQIAKAYARIGNSYFKEEKYKDAIHFYNKSLAEHRTPDVLKKCQQAEKILKEQERLAYINPDLALEEKNKGNECFQKGDYPQAMKHYTEAIKRNPKDAKLYSNRAACYTKLLEFQLALKDCEECIQLEPTFIKGYTRKAAALEAMKDYTKAMDVYQKALDLDSSCKEAADGYQRCMMAQYNRHDSPEDVKRRAMADPEVQQIMSDPAMRLILEQMQKDPQALSEHLKNPVIAQKIQKLMDVGLIAIR KR127C-21.3(SEQ ID NO: 9)IDNPTPKSSMTFKELYDEWLLVYEKEVQNSTYYKTTRAFEKHVLPVIGSTKLSDFTPMELQNFRNDLSEKLKFARKLFGMVRKVFNHAALLSYIQANPALPVTSQGIKLEHHHHHH MaR262-21.1(SEQ ID NO: 10)MPESYWEKVSGKNIPSSLDLYPIIHNYLQEDDEILDIGCGSGKISLELASLGYSVTGIDINSEAIRLAETAARSPGLNQKTGGKAEFKVENASSLSFHDSSFDFAVMQAFLTSVPDPKERSRIIKEVFRVLKPGAYLYLVEFGQNWHLKLYRKRYLHDFPITKEEGSFLARDPETGETEFIAHHFTEKELVFLLTDCRFEIDYFRVKELETRTGNKILGFVIIAQKLLEHHHHHHIMRFYGADDAIQSGEYQMPEIKVVK PaeKu (SEQ ID NO: 11)MARAIWKGAISFGLVHIPVSLSAATSSQGIDFDWLDQRSMEPVGYKRVNKVTGKEIERENIVKGVEYEKGRYVVLSEEEIRAAHPKSTQTIEIFAFVDSQEIPLQHFDTPYYLVPDRRGGKVYALLRETLERTGKVALANVVLHTRQHLALLRPLQDALVLITLRWPSQVRSLDGLELDESVTEAKLDKRELEMAKRLVEDMASHWEPDEYKDSFSDKIMKLVEEKAAKGQLHAVEEEEE VAGKGADIID

Each target sequence was then entered into the protein crystallizationserver, along with a PROF secondary structure prediction and a FASTAfile containing about 50 homologous protein sequences for each target.

Criteria used to select the epitope subsequences expected to improvecrystallizability of the proteins included: (1) prioritization byoverrepresentation ratio, using P-value cutoff; (2) prioritization ofmutations improving over-representation ratio at a given site (i.e.,avoiding removing an epitope subsequence with a better ratio than thenew epitope subsequence); (3) prioritization of epitope subsequencesobserved in packing interactions in at least 50 sequence-unrelatedproteins (“chainsets” as defined above) in the PDB; and (4) favoring ofsubstitutions maintaining or increasing polarity over those reducingpolarity.

The server outputted several hundred possible mutations that introduceone epitope from the epitope library at some position in the proteinsequence, with considerations given to primary and secondary structureconservation. The output list was ranked by the over-representationratio of each candidate epitope.

The researchers went down the list and use their knowledge of the targetprotein's biophysics and biochemistry to guide their selection ofepitopes, skipping epitopes that they believe would endanger theprotein's biological activity or structural stability. The researchersdecide whether they want to introduce a small and simple or a larger andmore complex epitope, and whether the suggested epitope mutation isbetter than any existing epitope it replaces. In addition to theseconstraints, the researchers use the epitopes' over-representationratios, P-values, in-epitopes fractions, non-homologous chainset counts,and non-water solvent fractions to decide which epitopes are better forthe given situation. The researchers are able to pick a few, several, ormany mutations from the candidates list to engineer in parallel,depending on the available resources and the degree of importance ofobtaining a structure.

Some of the engineered proteins and the recommended epitopes chosen forprotein expression and crystallization studies are shown in Table 38.

TABLE 38 (“Original Sequence” peptides disclosed as SEQ ID NOS 58-86 and“Sub-epitope” peptides disclosed as SEQ ID NOS 87-117, allrespectively, in order of appearance.) Sequence Original ID Number GenePosition Sequence Sub-epitope* 42 BhR182 11 YEEVA YxxxN/HHHHH 43 BhR182134 DRAKA ExxxR/HHHHH 44 BhR182 39 TLNPSF TxxxxR/CCHHHH 45 BhR182 12EEVAR YxxxR/HHHHH 46 BhR182 97 DETRRG DxxGxG/CCCCCC 2 CvR75A 90 AIVKRExxxR/HHHHH 13 CvR75A 19 DKMAD ExxxR/HHHHH 14 CvR75A 65 IRPLKYxxxQ/HHHHH 15 CvR75A 64 RIRP RxxE/HHHH 3 ER40 93 KxxxE 20 ER40 19 FSLLLFxxxQ/HHHHH 21 ER40 38 LALIR ExxxR/HHHHH 22 ER40 245 QAFG SAxG/HHHC 1HR4403 354 IKGYT ISxxT/CCHHH 4 KR127C 106 YKTEN 27 KR127C 76 KLFGMYxxxM/HHHHH 28 KR127C 55 FTPME LTxxE/CCHHH 29 KR127C 101 PVTSQGDxxGxG/CCCCCC 7 MaR262 38 GCGSG ACxxG 8 MaR262 129 RVLKPG RxxxPE 9MaR262 48 LASLGY LxxKxY 18 MaR262 188 KELVF KxxxE 6 SiR159 90 RMRARRxxxH/HHHHH 38 SiR159 44 KSLG SxxG/ECCE 39 SiR159 340 ARCG RxxG/HHCC 40SiR159 32 SQDAG SxxxH/HHHHH 41 SiR159 140 ADAPVQ LxxxxQ/CCHHHH 5 VpR106233 KQWLD QxxxD/HHHHH 16 VpR106 57 PLNRFQ LxxxxQ/CCHHHH 17 VpR106 60RFQNI ExxxR/HHHHH 19 VpR106 42 EAYKF ExxxR/HHHHH *Includes secondarystructure class: H = helix, E = β-strand and C is coil.

Example 3—Protein Expression and Crystallization Screening

Proteins from Example 2 are expressed, purified, concentrated to 5-12mg/ml, and flash-frozen in small aliquots as described in Acton et al.,Robotic cloning and Protein Production Platform of the NortheastStructural Genomics Consortium. Methods in Enzymology 394, 210-243(2005). All proteins contain short 8-residue hexa-histidine purificationtags (SEQ ID NO: 5,227) at their N- or C-termini and are metabolicallylabeled with selenomethionine. Matrix-assisted laser-desorption massspectrometry is used to verify construct molecular weight. All proteinsare ≥95% pure based on visual inspection of Coomasie Blue stainedSDS-PAGE gels. The distribution of hydrodynamic species in the proteinstock is assayed using static light-scattering and refractive indexdetectors (Wyatt, Inc., Santa Barbara, Calif.) to monitor the effluentfrom analytical gel filtration chromatography in 100 mM NaCl, 0.025%(w/v) NaN₃, 100 mM Tris-Cl, pH 7.5, on a Shodex 802.5 column (ShowaDenko, Tokyo, Japan). Protein samples are flash frozen in liquidnitrogen in small aliquots prior to crystallization or biophysicalcharacterization. Oligomeric state is inferred from the molecular weightdetermined by Debye analysis of the light-scattering data (Price et al.,Understanding the physical properties that control proteincrystallization by analysis of large-scale experimental data. NatBiotechnol 27 (1), 51-7 (2009)).

Initial high-throughput crystallization screening is conducted using the1,536-well microbatch robotic screen at the Hauptmann-Woodward Institute(Cumbaa et al., Automatic classification of sub-microliterprotein-crystallization trials in 1536-well plates. Acta Crystallogr.59, 1619-1627 (2003)). Proteins failing to yield rapidly progressingcrystal leads are subjected to vapor diffusion screening, typically300-500 conditions (Crystal Screens I & II, PEG-Ion and Index screensfrom Hampton Research or equivalent screens from Qiagen) at both 4° C.and 20° C. Screening is conducted in the presence of substrate orproduct compounds if commercially available.

Crystal optimization, diffraction data collection at cryogenictemperatures, structure solution using single or multiple-wavelengthanomalous diffraction techniques and refinement are conducted usingstandard methods.

Example 4—Analysis of Intermolecular Packing Interactions in the ProteinData Bank to Guide Rational Engineering of Protein Crystallization

X-ray crystallography is the dominant method for solving proteinstructures, but despite decades of methodological improvement, mostproteins do not yield solvable crystals. Even when selected using thebest algorithms available, at most 60% of proteins give crystals of anykind, and no more than 35% give crystals which can be solved. Thereasons for this low success rate remain obscure due to our limitedunderstanding of crystallization itself. A better understanding ofcrystallization is required to identify both problematic areas of theprocess and potential solutions to this critical barrier. Working withinthis framework, and as described herein, is a characterization thestereochemical features of crystal packing interactions to guiderational engineer protein sequences to improve crystallization.Described herein is a rigorous parsing of all protein crystal structuresin the Protein Data Bank (PDB) to identify and characterize crystalpacking patterns. All residues within a minimum contact distance betweenchains are identified and then grouped into an ascending hierarchyranging from the simplest elementary binary interacting epitopes tocomplete binary interprotein interaction interfaces. For counting andaveraging purposes, protein chains are redundancy-downweighted toaccount for homologous chains forming similar crystals, as evaluated bya dot-product-like Packing Similarity Score. Also described herein is anidentification of sequences which appear disproportionately frequentlyin packing interfaces relative to their background frequency in the PDB.These overrepresented sequences are more efficacious at formingfavorable packing interactions, and therefore offer attractivepossibilities for new engineering approaches to enhance proteincrystallizability.

More than 50 years after the solution of the first protein crystalstructure Kendrew, et al., Nature 1958, 181 (4610), 662-6), proteincrystallization remains a hit-or-miss proposition. However, as long asmost proteins cannot be crystallized, crystallization fundamentallyremains a hit-or-miss proposition. Synergistic developments incrystallographic methods, synchrotron beamlines, and high-speedcomputing have made structure solution and refinement routine, even forvery large complexes, as long as high-quality crystals are available.However, there has been comparatively little progress in improvingmethods for protein crystallization. Recent work by structural genomics(SG) consortia has systematically confirmed that most naturallyoccurring proteins do not readily yield high-quality crystals suitablefor x-ray structure determination and that crystallization is the majorobstacle to the determination of protein structures using diffractionmethods (Canaves, et al., Journal of molecular biology 2004, 344 (4),977-91; Slabinski, et al., Protein Sci 2007, 16 (11), 2472-82). Manyimpressive technological innovations during the last 20 years havesimplified and streamlined the work involved in protein crystallization.These include the development of highly efficacious chemical screensthat mimic historically successful crystallization conditions (Price, etal., Nat Biotechnol 2009, 27 (1), 51-7), sophisticated robotics thatenable more crystallization conditions to be screened with less proteinand effort (Cooper, et al., Acta crystallographica 2007, 63 (Pt 5),636-45; Derewenda, Methods 2004, 34 (3), 354-63), and numerous otherclever innovations that improve the crystallization process in somecases. Even with these advances, only approximately ⅓ of proteins witheven the most promising sequence properties yield crystal structuresfrom a single protein construct.

Existing methods for engineering improved protein crystallization workwith limited efficiency. Consistent with this premise, changes inprimary sequence have been demonstrated to substantially alter thecrystallization properties of many proteins (Derewenda, Actacrystallographica 2006, 62 (Pt 1), 116-24; Stanley, Science (New York,N.Y. 1935, 81 (2113), 644-645). Disordered backbone segments can beidentified using elegant hydrogen-deuterium exchange mass spectrometrymethods, and genetically engineered constructs with such segmentsexcised have shown improved crystallization properties (Edsall, Journalof the history of biology 1972, 5 (2), 205-57). Progressive truncationof the N- and C-termini of the protein can also yield crystallizableconstructs of proteins that initially failed to crystallize (Hunt andIngram, Nature 1958, 181 (4615), 1062-3). However, many nestedtruncation constructs generally need to be screened, sometimes withtermini differing by as little as two amino acids, and this procedurestill frequently fails to yield a soluble protein construct producinghigh-quality crystals. The Surface Entropy Reduction (SER) methoddeveloped by Derewenda and co-workers uses site-directed mutagenesis toreplace high-entropy side chains on the surface of the protein(generally lysine, glutamate, and glutamine) with lower entropy sidechains (generally alanine) (Derewenda, Acta crystallographica 2006, 62(Pt 1), 116-24; Stanley, Science (New York, N.Y. 1935, 81 (2113),644-645; Lessin, et al., J Exp Med 1969, 130 (3), 443-66). In most casesin which a substantial improvement in crystallization has been obtainedby this method, a pair of such mutations were introduced at adjacentsites. While some spectacular successes have been obtained this way,most such mutations reduce the solubility of the protein, frequently soseverely that a high quality protein preparation can no longer beobtained. Most attempts to employ this technique in the Hunt lab haveresulted in production of insoluble protein (unpublished results). TheDerewenda group has also evaluated the use of amino acids other thanalanine to replace high-entropy side chains (Derewenda, Actacrystallographica 2006, 62 (Pt 1), 116-24; Kendrew, et al., Proc R SocLond A Math Phys Sci 1948, 194 (1038), 375-98). These substitutionsfrequently change the crystallization properties of the protein, but sofar, there is no report of such alternative substitutions being used toefficiently engineer crystallization of an otherwisecrystallization-resistant protein.

Recent large-scale experimental studies have shown that the surfaceproperties of proteins, and particularly the entropy of the exposed sidechains, are a major determinant of protein crystallization propensity(Slabinski, et al., Protein Sci 2007, 16 (11), 2472-82). These studiesdemonstrated that overall thermodynamic stability is not a majordeterminant of protein crystallization propensity. They also identifieda number of primary sequence properties that correlate withcrystallization success, including the fractional content of severalindividual amino acids. Unfortunately, further studies have demonstratedthat every individual amino acid that positively correlates withcrystallization success negatively correlates with protein solubility,and vice versa. This effect severely limits the efficacy of using singleamino acid substitutions to engineer improved protein crystallizationbecause crystallization probability is low unless starting with amonodisperse soluble protein preparation. Moreover, hydrodynamicheterogeneity and aggregation, which are correlated with low solubility,significantly impede crystallization (Slabinski, et al., Protein Sci2007, 16 (11), 2472-82; Edsall, Journal of the history of biology 1972,5 (2), 205-57). Therefore, any engineering strategy focused onsingle-residue substitutions is likely to suffer from problems withprotein solubility, as has been observed for the Surface EntropyReduction method (Stanley, Science (New York, N.Y. 1935, 81 (2113),644-645; Lessin, J Exp Med 1969, 130 (3), 443-66; Ferre-D'Amare,Structure 1994, 2 (5), 357-9). More complex approaches than singleamino-acid substitutions are needed for efficient engineering ofimproved protein crystallization.

Described herein is an analysis of crystal-packing interactions in theProtein Data Bank based on a new analytical framework specificallydeveloped to support rational engineering of improved proteincrystallization. Also described herein are results demonstrating suchapproaches based on introduction of more complex sequence epitopes thathave already been observed to mediate high-quality packing contacts incrystal structures deposited into the Protein Data Bank (PDB). Manynaturally occurring proteins have excellent solubility properties andalso crystallize very well. The results described herein show thatspecific protein surface epitopes can mediate strong interproteininteractions under the special solution conditions that drive proteincrystallization without compromising solubility in the dilute aqueousbuffers used for protein purification.

Beyond providing a library of previously observed linear crystal-packingepitopes, this analysis provides new insight into the physiochemicalproperties of protein crystals. Packing interactions typically involveapproximately half of all residues on the protein surface, and areextremely polymorphic among proteins with very high homology, even thosewith nearly identical cell unit cell constants. However, there areindications that some sequences can preferentially mediate high-qualitypacking interactions. Furthermore, most isolated packing epitopes aresmall in size and extent, suggesting that they may be feasible targetsfor engineering efforts.

Example 4—Identification and Analysis of Sequence Epitopes MediatingInterprotein Packing Interactions in the PDB

Described herein is a hierarchical analytical scheme to identifycontiguous epitopes potentially useful for protein engineering (FIG. 3).This scheme is used to analyze all interprotein packing interactions incrystal structures in the PDB (FIG. 5). The hierarchical scheme is atthe heart of our analysis. As used herein, an interface refers to allresidues making atomic contacts (≤4 Å) between two protein moleculesrelated by a single rotation-translation operation in the real-spacecrystal lattice. The interface is decomposed into features that we callElementary Binary Interaction Epitopes (EBIEs—top of FIG. 3). Thesecomprise a connected set of residues that are covalently bonded or makevan der Waals interactions to one other in one molecule and that alsocontact a similarly connected set of residues in the other moleculeforming the interface. EBIEs are the foundation of the analysisdescribed herein because they represent potentially engineerablesequence motifs. One or more EBIEs that are connected to one another bycovalent bonds or van der Waals interactions within a molecule form aContinuous Binary Interaction Epitope (CBIE). One or more CBIEs in onemolecule that are connected to one another indirectly by a chain ofcontacts across a single interface form a Full Binary InteractionEpitope (FBIE). The set of one or more FBIEs that all mediate contactsbetween the same two molecules in the real-space lattice form a completeinterface (bottom of FIG. 3).

The results of applying this analytical scheme to the entire PDB areshown in FIG. 5. On average, approximately half of all surface-exposedresidues participate in crystal packing interactions (FIG. 5B). Proteinchains form a plurality of interfaces each, with many more non-properinterfaces than proper interfaces formed (FIG. 5C). The set of properinterfaces, which are more likely to be oligomers or biologicalinterfaces, contains many more larger interfaces than nonproperinterfaces (FIG. 5D). However, while these data describe the compositionof the crystal structures in the PDB as a whole, they do not addresscomplications raised by nonhomogoneities within the population of thePDB. In particular, two issues need to be addressed. First, FIG. 5B-Dshows that proper interfaces behave significantly differently fromnonproper interfaces, indicating that they should be segregated foranalysis. Second, the PDB contains many structures which are partiallyor completely redundant, which creates small inaccuracies in thecharacterization of structures in general but much larger problems inthe eventual identification of sequence motifs which are overrepresentedin crystal packing interactions. As described herein, both of theseconcerns are addressed by computational flagging and downweightingmechanisms.

The BioMT database, which categorizes all previously describedbiological interfaces in the PDB, was used to identify biologicaloligomers. Interfaces so identified were flagged as “BioMT” interfaces.Recognizing that some potential oligomeric interfaces may not beappropriately categorized by BioMT, the set of “proper” interfaces whichcould be either biological or crystallographic were also identified.

Interfaces were designated as “proper” if they form part of a regularoligomer with proper rotational symmetry (i.e., n protein molecules inthe realspace lattice each related to the next by a 360°/n rotation±5°,with n being any integer from 2-12) and “non-proper” if they do not.Proper interfaces could potentially be part of a stable physiologicaloligomer while non-proper interfaces cannot. After these twocategorization steps, four sets of interfaces exist: the set of allinterfaces; the set of biological interfaces identified by BioMT; theset of proper interfaces not identified as biological interfaces byBioMT, but which could potentially be either biological orcrystallographic; and the set of interfaces which are not identified byBioMT and which are not proper, as defined above. The most conservativeapproach to isolating non-physiological crystal packing interactions isto focus exclusively on non-proper interfaces in order to exclude anycomplex that is potentially a physiological oligomer. Nonetheless,epitopes that contribute to stabilizing physiological oligomers maystill be useful for engineering purposes, and epitopes that promoteformation of a regular oligomer would be particularly useful becausestable oligomerization strongly promotes crystallization (Slabinski,Protein Sci 2007, 16 (11), 2472-82).

Even when all biological and oligomeric interfaces have been removedfrom the dataset, significant redundancy remains within the PDB. Manyproteins in the PDB have had multiple crystal structures deposited,which may have very similar if not identical packing interactions (e.g.,multiple mutations at a non-interacting active site) but which can alsohave completely separate packing interactions (e.g., crystallizationunder different conditions into a different crystal form). Simplyculling identical or homologous proteins would remove all redundancy butwould also eliminate significant information from the second situation,where the same protein forms crystals with different packinginteractions. To implement a redundancy down-weighting, the PackingSimilarity Score (PSS) was developed to evaluate the similarity betweeninterprotein interfaces, full chain interactions, and crystals. PSS iscalculated in the following way (more details are included in Methods):Interactions matrices are generated for each interface, with rowsrepresenting residues in one chain and columns representing residues inthe other chain. Cells in the matrix include the number of interatomiccontacts between the two residues (including bonds mediated by a singlesolvent molecule) and the B-factor-derived weight associated with thatcontact. The PSS between two interfaces is defined as the Frobeniusproduct (essentially a matrix dot-product) of the two sequence-alignedinteraction matrices, normalized to a range between 0 and 1. This valuecontains significant information about the overall similarity of twointerfaces, and is sensitive to small changes; it also necessarilyencodes the more basic information about the fraction of preservedresidues (FIG. 4A). To calculate the PSS for two chains or two crystals,the process is essentially repeated on a larger scale. Each interface inone chain is matched with an interface in the second chain with which ithas the highest PSS. Interfaces are ordered in this way, and theindividual interaction matrices are then inscribed into the largerchain/chain or crystal/crystal interaction matrix. The Frobenius productof this matrix is then taken. However, since best-matches are notnecessarily reciprocal, the best-interface-matching process is repeatedin reverse to ensure reciprocality of the chain or crystal PSS. TheFrobenius products of the two matrices are added and then normalized togive the chain or crystal PSS.

FIG. 4 shows statistics from application of this analytical scheme toall crystal structures in the PDB (39,208 entries). The average numberof total, proper, and non-proper interfaces per protein molecular are6.9, 1.8, and 5.1, respectively (FIG. 5A). While a minimum of fourinterfaces are required for a single molecule to form a 3-dimensionallattice, fewer are possible when multiple molecules are present in thecrystallographic asymmetric unit. Proteins generally contain only asmall number of interfaces beyond the minimum required for latticeformation, indicating that most interfaces contribute to structuralstabilization of the lattice. On average, 50% of surface-exposedresidues and 36% of all residues participate in interprotein packinginteractions (FIG. 5B). While interfaces range widely in size, 36% ofall interfaces and 42% of non-proper interfaces contain 10 or fewerresidues counting contributions from both sides of the interface (˜5from each participating molecule) (FIG. 5C). The small size of theaverage interface is encouraging relative to the feasibility ofengineering interface formation. Half of all interfaces are under eightresidues in size, and a quarter (8678 total) are under eight residues inrange within the polypeptide chain (separation). The cumulativesize/range distributions for all interfaces, CBIEs, and EBIEs (FIG. 5D)shows that most interfaces are topologically simple and local in theprimary sequence, even though some are complex. It is noteworthy thatFBIE's contain on average fewer than two EBIEs (not shown) and that mostEBIEs are less than 4 residues in size and 10 residues in range. Thesesmall EBIEs represent prime candidates for engineering improvedcrystallization of crystallization-resistant proteins.

Quantifying similarity in the crystal-packing interactions of homologousproteins demonstrates pervasive polymorphism in interprotein interfaces.A general method was developed to quantify the similarity betweendifferent interprotein packing interfaces formed by homologous proteins.Its foundation is a B-factor-weighted count (C_(ij)) of inter-atomiccontacts between residues i and j across the interface:

$C_{ij} = {\sum\limits_{{atom}.{pairs}}\;( \frac{\langle B \rangle_{2 - {10\%}}}{\sqrt{B_{m}B_{n}}} )^{n}}$

The terms B_(m) and B_(n) are the atomic B-factors of the contactingatoms in residues i and j, respectively (i.e., atoms with centersseparated by less than 4 Å), while <B>₂₋₁₀% represents an estimate ofthe B-factor of the most ordered atoms in the structure (which iscalculated as the average B-factor of atoms in the 2nd through 10^(th)percentiles). An upper bound of 1.0 is imposed on the B-factor ratio(i.e., it is set to 1.0 whenever (B_(m)B_(n))^(1/2)<<B>₂₋₁₀%). Theexponent n is an adjustable parameter in our software that allowsanalyses to be performed either without (n=0) or with (n≥1)down-weighting of contacts between atoms with high B-factors. Suchatoms, which have enhanced disorder, may contribute less to interfacestabilization, but prior literature on this topic is lacking. Therefore,we developed an analytical approach facilitating exploration of B-factoreffects. Specifically, using higher values of n in our scoring functionprogressively down-weights high B-factor contacts.

Each interface in a crystal structure (as defined above) isquantitatively described by a contact matrix C containing thecorresponding C_(u) values (i.e., with its rows and columns indexed bythe residue numbers in the two interaction proteins). To evaluate thesimilarity in interprotein interfaces formed by homologous proteins,their sequences are aligned using the program CLUSTAL-W (Mateja, Actacrystallographica 2002, 58 (Pt 12), 1983-91) (after transitivelygrouping together all proteins sharing at least 60% sequence identity).This procedure effectively aligns both the columns and rows in thecontact matrices for interfaces formed by the homologous proteins. ThePacking Similarity Score (PSS) between the interfaces is then calculatedas the Frobenius (matrix-direct) product between the respective contactmatrices. This procedure is mathematically equivalent to calculating adot-product between vectors filled with the contact count betweenresidue pairs in the interfaces. PSSs value ranges from 1.0, if thenumber of contacts between each interfacial residue pair is identical,to 0.0, if no pairwise contacts are preserved.

This metric was used to analyze a dataset comprising all pairs ofcrystal structures in the PDB containing proteins with ≥98% sequenceidentity (FIG. 4C). This dataset includes a heterogeneous mixture ofmutant/ligand-bound structures in the same spacegroup as well asalternative crystal forms of the same protein. While many interfaces areapproximately conserved, it is rare for identical packing interactionsto be observed in different crystal structures of nearly identicalproteins. While 35% of interfaces show PSSs of 0.80-0.95, another 30%have PSSs from 0.40-0.80. Therefore, there is almost invariably somedegree of plasticity in interfacial packing contacts and frequentlysubstantial polymorphism. Importantly, the residues involved incrystal-packing interactions tend to be conserved (˜50% over randomexpectation) even when pairwise interactions in the interface are notconserved. This observation indicates that some surface residues haveinherently high crystallization-packing potential, so introducingcorresponding epitopes into a protein is likely to increase itscrystallization propensity even if the complementary epitope is notpresent.

The observation that some interfacial contacts are preserved, whileother are not, leads to a series of important conceptual and practicalconclusions. Most importantly, conservation of packing similarityprovides experimental data on the strength of the different packingcontacts within an interface, because energetically more stable contactsare less likely to be perturbed to satisfy differences in thephysiochemical environment in different crystals. The results andmolecular-mechanics calculations described herein show that the morepreserved packing contacts have higher thermodynamic stability than theless preserved contacts. These contacts with higher stability are likelyto play an important role in specifying and stabilizing the crystallattice, and are therefore prioritized for evaluation inepitope-engineering experiments. Some residues contribute more thanothers to stabilization of crystal packing-interactions in thermodynamicdissection of interprotein interfaces in stable complexes (Jaroszewski,Structure 2008, 16 (11), 1659-67). Residues making packing contacts withlower stability nonetheless need to be immobilized upon interfaceformation, which will incur a substantial entropic penalty that could belarger than their favorable contribution to the formation of crystalinterfaces. In this context, it is not surprising that crystallizationis thermodynamically finicky and very sensitive to the mean entropy ofsurface-exposed side chains (Derewenda, Acta crystallographica 2006, 62(Pt 1), 116-24).

Mutation of surface-exposed residues is likely to induce changes incrystal packing whether they participate in either high-stability or lowstability contacts. This effect, combined with the fact that 60% of thesurface-exposed residues in the average protein make interfacialcontacts (FIG. 5A), rationalizes the fact that surface mutations veryfrequently change crystallization behavior and that proteins with lessthan 90% sequence identity only form similar non-proper packinginterfaces very infrequently (FIG. 5C). However, engineering improvedcrystallization behavior requires introduction of epitopes with apropensity to form high-stability crystal-packing contacts.

Creation of a library of all linear sequence epitopes mediatingcrystal-packing interactions in the PDB and to develop metrics to scoretheir packing potential. We have created a database containing a libraryof all EBIEs, CBIEs, and FBIEs in the PDB that span at most twosuccessive regular secondary structural elements and flanking loops (asidentified by the DSSP algorithm (Wukovitz, Nat Struct Biol. 1995, 2(12), 1062-7)). The sequence of both contacting and non-contactingresidues is stored along with the standard DSSP-encoding of thesecondary structure at each position in the protein structure in whichthe epitope was observed to mediate a crystal packing interaction. Allmetrics possibly related to the crystal-packing potential of the epitopeare recorded, including B-factor distribution parameters, statisticalenrichment scores relative to all interfaces in the PDB as well asconservation in multiple crystals from homologous proteins, andcrystallization propensity and solubility scores based on the sequencecomposition of the epitope. The database includes the identity of allEBIE pairs making contact with each other as well as a breakdown of thecomposition of all FBIEs and CBIEs in terms of their constituent EBIES.

Computational analyses of crystal-packing interactions in the PDB toidentify short epitopes with statistically enhanced occurrence incrystal-packing interfaces. This library is used to count all EBIEswhich appear in the PDB, and to determine which sequences arestatistically overrepresented in EBIE's given their background frequencyin non-interacting sequences in the PDB.

Prior to considering specific amino acid sequences, the secondarystructure patterns which appeared most frequently in EBIEs wereexamined. Some secondary structure patterns appeared much morefrequently than others; these are summarized in Table 2.

Example 6—Epitope-Engineering Experiment

The methods described herein were used to select putativecrystallization-enhancing epitopes for six target proteins that yieldedunsolvable crystals and another three that never yielded crystals of anykind with their native sequences (FIG. 9 & FIG. 10). After making anaverage of three epitope mutations per protein, crystal structures wereobtained for five of the six proteins that yielded unsolvable crystalswith their native sequences (FIG. 9). Furthermore, crystals for two ofthe four proteins that failed to yield any crystals with their nativesequences were also obtained. Both 1.9 Å and 1.8 Å diffraction wasobtained for these two proteins respectively, and both datasets led tosolved crystal structures (FIGS. 15-16). All of the amino-acidsubstitutions that produced crystal structures involved substitution ofa residue with higher sidechain entropy than the residue it replaced inthe native sequence. In three cases, the successful mutation involvedintroduction of lys or glu residues, exactly the residues that areremoved in classic surface-entropy reduction. Therefore, whileengineering low surface entropy is one consideration underlying themethods described herein, the design strategy focusing on tertiaryepitopes leads to fundamentally different kinds of amino acidsubstitutions than used in previous surface-entropy reduction methodsinvolving substitution of individual amino acids with low sidechainentropy, which are generally more hydrophobic and impair proteinsolubility. In contrast, in the results described herein, 39 of 41mutant proteins (95%) were sufficiently stable and soluble to undergohigh-throughput crystallization screening (FIGS. 10 A and B). Only twoof these were significantly destabilized compared to the native sequencebased on Thermofluor analyses (FIG. 10C). The vast majority produced asignificant increase in the number of crystallization hits in systematichigh-throughput screening (FIG. 10D). One crystal structure was obtainedfrom a mutant that reduced the total number of hits but produced hitsunder alternative chemical conditions. This property was shared by 28 of32 screened mutant proteins, i.e., they yielded at least some andtypically many “hits” under alternative conditions than the WT protein(FIG. 10E). Two of the five crystal structures generated from mutantproteins show the mutated residue making a direct contact in a packinginterface (e.g., FIG. 10F), although with somewhat differentstereochemistry from the template used for engineering. The thirdstructure shows the mutant residue contacting an adjacent residue thatmakes a crystal packing contact. However, the fourth structure shows themutant residue in a region of weak electron density, while the fifthshows it to be relatively remote from any packing interface.

An advantage of the methods described herein is its very high yield ofsoluble protein variants, which enable the search for chemicalconditions mediating stable lattice formation to be conducted withproteins with a greater diversity of surface properties that aregenerally favorable for crystallization. This newcrystallization-screening “variable”, which can be explored efficientlywith the methods describes herein, enables more effective exploitationof the thermodynamic forces promoting crystallization during extensivechemical screening.

Example 7—Epitope Sub-Distributions

B-factor distributions in sub-epitopes can also be evaluated as afunction of overrepresentation ratio, structure resolution, residuetype, epitope size, buried surface area, and proportional contributionto an interface in connection with the methods described herein. Suchanalysis can be used to design of ranking metrics using sub-epitopeB-factor distributions.

Analyses of topological, energetic, and primary sequence differencesbetween non-BIOMT/non-proper crystal packing interactions and BIOMTinterfaces mediating stable protein oligomerization, can also be used inconnection with the methods described herein. Such analyses can be usedto determine whether ranking metrics excluding BIOMT interfaces improveoutcome.

Several reference databases can be generated in addition to the1-to-6-mer sub-epitope database described herein (EEDb1). One suchreference database can be used to restrict overrepresentationcalculations and engineering suggestions to sub-epitopes withsurface-exposed residues at all contacting positions (EEDb2). Otherreference databases can be used to restrict consideration to completeEBIEs rather than including sub-epitopes (EEDb3). Yet another referencedatabase could be limited to single amino acids in a specific secondarystructure as presented in FIG. 18.

The epitope-engineering methods described herein can be adapted foralpha-helical integral membrane proteins (IMPs). This adaptation can beperformed by adding a second mask to the specification of each epitopeindicating whether it resides in a transmembrane alpha-helix. Theepitope distributions observed in the crystal structures ofalpha-helical IMPs can be compared to those in the full PDB and thedistribution of packing contacts relative to the centroids and thetermini of the transmembrane α-helices can be analyzed. The observedpatterns can be used to customize epitope-engineering suggestions forα-helical IMPs.

Example 8—Introduction of Salt Bridges Improve Crystallization

One of the most overrepresented dimeric crystallization sub-epitopes inthe PDB comprises a glu-arg salt-bridge on the surface of an α-helix(ExxxR (SEQ ID NO: 50)/HHHHH in Table 37). Introduction of thissub-epitope into predicted alpha-helices in crystallization-resistantproteins can improve their crystallization sufficiently to yield astructure.

Four NESG proteins that have given crystals with at best poordiffraction (4-8 Å limiting resolution at the synchrotron) and anotherfour that have never given a crystallization hit were selected foranalysis. These eight proteins were mutated to introduce new glu-argsalt-bridges at 4 different sites in predicted alpha-helices. The mutantproteins were expressed and analyzed for their solubility, stability,and hydrodynamic homogeneity and subjected to crystallization screeningand optimization using the standard NESG platform. All relatedexperimental data were systematically evaluated to determine whether anyof the sequence parameters and computational metrics correlated withoutcome at every stage of the pipeline (i.e., expression, solubility,stability, and crystal-structure solution.)

Example 9—Introduction of Other Epitopes Improve Crystallization

Similarly designed studies will be conducted on four other highlyoverrepresented dimeric sub-epitopes shown in Table 37. Another studywill focus on introducing 20 different candidate sub-epitopes into eachof two poorly crystallizing proteins to evaluate correlations betweenprotein expression/crystallization outcome and all computed rankingmetrics. Another study will take a similar approach to determiningwhether efficacy is improved by limiting engineering to complete EBIEsrather than using sub-epitopes. Based on the results obtained from theseinitial studies, additional studies will be designed to further explorethe efficacy of alternative crystallization-epitope-engineeringstrategies.

Example 10—Effects of Epitope Engineered Single and Poly Mutant Proteinson Protein Solubility

The introduction of crystallization-inducing epitopes can also haveeffects on other protein characteristics, such as solubility. To comparethe solubility of the wildtype protein VCR193 to its epitope mutants,each VCR193 construct was subjected to a precipitant solution ofammonium sulfate at varying concentrations, and after a period ofincubation, soluble protein levels tested with a NanoDrop 200 UV-VisSpectrophotometer.

All protein stock concentrations were determined using the NanoDrop 2000at A280. A stock solution of precipitant (3M NH4SO4) was prepared inExperimental buffer (50 mM sodium acetate, pH 4.25). Using these stockconcentration values, mixtures of varying protein and precipitantconcentrations were prepared in 1.5 mL Eppendorf tubes at roomtemperature. For each construct, final protein concentrations of 1, 2and 4 mg/mL were mixed with final precipitant concentrations of 0.8,1.0, 1.2 and 1.4M NH4SO4. Experimental buffer was used to bring eachaliquot to a final volume of 50 uL. For all samples, components wereintroduced in the order of precipitant, buffer, and protein. All sampleswere performed in duplicate. Once all mixtures were prepared, sampleswere incubated at room temperature for 5 minutes, then transferred to abenchtop microcentrifuge. Samples were spun for 2 minutes at 13.4K RPMto pellet any precipitation. Sample supernatants were then tested forremaining soluble protein with the NanoDrop 2000.

Results show that for the 4 single mutants designed for VCR193, only one(VCR193_F241R) had a detrimental effect on protein solubility (FIG. 12)Notably, the mutation reducing solubility was the only one among the settested to significantly destabilize the protein thermodynamically. Allother mutants maintained, or showed a slight increase (VCR193_V122R) inprotein solubility.

Similar results were seen for the poly-mutant samples (FIG. 13). Proteinsolubility was not affected, except in the one poly mutant thatcontained the VCR193_F241R mutation which had previously shown adecrease in solubility.

Example 11—Combining Multiple Epitope Mutations can Produce AdditionalLarge Gains in Crystallization Propensity Over the IndividualConstituent Mutations

Purified proteins were set up in a standard robotic microbatchcrystallization screen. The screen covered 1536 different chemicalconditions. Observations were reported after one week of incubation at4° C., based on robotic imaging of the reactions and manual evaluationof the resulting optical micrographs. The results in FIG. 14 demonstratethat the epitope mutations in this protein generally increase the numberof crystallization hits and always yield hits under differentcrystallization conditions than the WT protein. Combining multipleepitope mutations increases further the number of hits obtained,indicating that this “multimutant” crystallizes more avidly than theindividual epitope mutant.

Example 12—Epitope-Engineering Study on “No Hits” Proteins

Proteins were selected with Pxs≥0.25, monodisperse stocks, and cleanThermofluor melts. Four proteins that showed no evidence ofcrystallization with their native sequences in the 1536 well screen werere-purified and put through the 1536 well screen a second time, toverify their failure to crystallize prior to the generation of mutants.Four or five epitope mutations, primarily introducing salt-bridges, werethen introduced into each protein, and the resulting mutant variantswere purified and analyzed, yielding results summarized in FIG. 15. Ofthe 18 mutations for which data are presented, 16 essentially preservedthe stability and solubility of the protein. Single epitope mutationsyielded very high quality crystal structures for two of the fourproteins in the study. The results show that epitope mutations producingcrystal structures are located in packing contacts. The mutated residuesmake direct or water-mediated hydrogen-bonds in one of thecrystal-packing interfaces in these structures, as shown for proteinLpYceA (LgR82) in FIG. 16 on the right. Any failures were either large(>400 aa) or yielded aggregation-prone proteins upon mutation.Additional epitope mutations can be introduced into stable di- andtri-mutants of failures.

Example 13—Overrepresentation of Individual Amino Acids in SpecificSecondary Structures in Packing Interfaces in the PDB

After normalization for the abundance of the amino acids on proteinsurfaces in the PDB (“surface-shaping”), the number of amino acids ineach secondary-structure class making crystal-packing interactions wascounted and compared to random expectation. FIG. 18 shows theover-representation ratios calculated in this manner for the 60 classes(20 amino acids in three possible secondary structures—H, E, and L forhelix, strand, and “loop”, respectively). FIG. 19 presents the samevalues plotted against the solvent-accessible surface area of thesidechain of each amino acid, which shows that amino acids withcomparable surface area have significantly different propensity tomediate crystal-packing interactions. Notably, many of the most stronglyoverrepresented residues in crystal-packing interfaces have a negativeinfluence (e.g., gln, glu, or lys in helices) or a neutral influence(arg in helices) on crystallization propensity when overallamino-acid-frequency on the protein surface is analyzed. Therefore, thedata presented in these slides demonstrate that the structural contextof individual amino acids has a critical effect on their propensity tomediate crystal-packing interactions. These results demonstrate that theepitope library described herein is successful in identifying the propercontext, as evidenced by the data obtained in experiments introducingthese epitopes into crystallization-resistant proteins. This contextfrequently involves high-entropy polar side chains being constrained bylocal entropy-reducing structural interactions. Notably, the amino acidssubstitutions that have been most successful in yielding crystalstructures in these experiments (i.e., glu and arg in helices) are amongthe most strongly overrepresented in crystal-packing interfaces oncesecondary structure is taken into account, as shown in FIG. 18.Therefore, one reason that our methods are successful in improvingprotein crystallization is that they guide insertion at productivelocations of amino acids that have a high propensity to mediatecrystal-packing interactions when present in the right structuralcontext.

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APPENDIX A

TABLE 4 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio Probability RH 73875.0 56304.4 135926.2 96.749968 0.0000e+00 1.00000 N 0.5434930.414228 E H 102063.2 85694.0 211404.9 72.514212 0.0000e+00 1.00000 N0.482785 0.405355 R C 71101.6 59909.4 138577.7 60.689664 0.0000e+001.00000 N 0.513081 0.432316 Q H 48815.1 39519.7 106533.5 58.9548880.0000e+00 1.00000 N 0.458214 0.370961 K H 75386.1 65574.6 154046.450.558309 0.0000e+00 1.00000 N 0.489373 0.425681 R E 31731.5 25548.465634.9 49.498779 0.0000e+00 1.00000 N 0.483455 0.389250 Y C 29955.125200.3 79918.7 36.198231 3.7253e−287 1.00000 N 0.374820 0.315324 Y H22863.8 18907.6 77770.4 33.070975 4.4619e−240 1.00000 N 0.2939910.243121 N C 74926.0 68249.9 172909.9 32.846465 6.9358e−237 1.00000 N0.433324 0.394714 Y E 20348.1 16817.5 77792.9 30.751543 6.6667e−2081.00000 N 0.261568 0.216182 H H 17545.3 14723.1 46812.1 28.0924726.9628e−174 1.00000 N 0.374803 0.314515 W C 9843.2 7836.3 28898.726.555390 1.3266e−155 1.00000 N 0.340610 0.271165 W E 7175.4 5519.128478.8 24.830813 2.5110e−136 1.00000 N 0.251956 0.193796 N H 29380.126250.3 74966.1 23.963336 3.6776e−127 1.00000 N 0.391912 0.350162 Q C46688.9 43067.7 104526.3 22.756429 6.6571e−115 1.00000 N 0.4466710.412027 D H 48052.3 44330.5 115744.8 22.503742 2.0419e−112 1.00000 N0.415157 0.383002 Q E 16054.3 13925.4 44387.5 21.776876 2.1490e−1051.00000 N 0.361685 0.313724 E E 27514.1 24818.0 68285.5 21.4505132.4598e−102 1.00000 N 0.402927 0.363444 K C 84342.9 80316.9 179173.619.124939 8.1926e−82 1.00000 N 0.470733 0.448263 W H 8266.4 6969.234240.4 17.410753 3.8441e−68 1.00000 N 0.241422 0.203539 F C 25086.122981.3 88412.8 16.139207 7.1968e−59 1.00000 N 0.283738 0.259932 P H20437.9 18997.4 55888.0 12.864046 3.7994e−38 1.00000 N 0.365694 0.339919K E 30928.1 29266.2 72555.6 12.576763 1.4865e−36 1.00000 N 0.4262680.403362 H E 9540.2 8591.3 33198.0 11.890730 7.1273e−33 1.00000 N0.287373 0.258790 F E 14087.0 13074.4 85656.9 9.620803 3.4203e−221.00000 N 0.164458 0.152636 E C 80396.1 78595.3 181587.9 8.5294037.5074e−18 1.00000 N 0.442739 0.432822 X H 360.8 254.8 654.5 8.4977621.3638e−17 1.00000 N 0.551261 0.389301 X E 156.4 96.6 287.5 7.4715896.3554e−14 1.00000 N 0.544000 0.335882 X C 819.5 684.6 1607.8 6.8031256.0965e−12 1.00000 N 0.509703 0.425809 F H 16970.0 16250.6 93022.46.212142 2.6862e−10 1.00000 N 0.182429 0.174695 D C 92573.2 91722.3226663.0 3.641120 1.3686e−04 0.99987 N 0.408418 0.404664 N E 12244.911913.0 40730.7 3.614854 1.5345e−04 0.99985 N 0.300631 0.292483 S H34149.8 34223.3 112014.7 −0.476652 0.68435 0.31796 N 0.304869 0.305525 CC 8790.4 8862.7 38092.8 −0.876297 0.81121 0.19209 N 0.230763 0.232660 DE 13940.8 14199.4 46856.3 −-2.599200 0.99540 4.7409e−03 N 0.2975220.303041 M H 11582.9 12155.3 61070.7 −5.801564 1.00000 3.3857e−09 N0.189664 0.199037 M E 5267.8 5774.1 33368.7 −7.327132 1.00000 1.2408e−13N 0.157867 0.173040 P E 7858.0 8602.7 29317.0 −9.552002 1.000006.7668e−22 N 0.268036 0.293438 C H 3384.9 4013.8 27016.9 −10.7577871.00000 2.9878e−27 N 0.125288 0.148566 T H 25364.6 26858.9 95207.8−10.761143 1.00000 2.7304e−27 N 0.266413 0.282108 P C 79479.4 82017.5226569.8 −11.095397 1.00000 6.7670e−29 N 0.350794 0.361997 C E 3054.03879.2 30999.5 −14.164659 1.00000 8.5647e−46 N 0.098518 0.125137 I C24372.0 26598.2 100435.4 −15.920127 1.00000 2.4323e−57 N 0.2426630.264829 T C 60897.2 64345.5 175852.7 −17.071578 1.00000 1.2602e−65 N0.346297 0.365906 S E 18279.6 20897.6 82683.2 −20.949793 1.000001.0248e−97 N 0.221080 0.252742 L C 48520.1 52756.1 185873.9 −21.7924931.00000 1.4458e−105 N 0.261038 0.283827 T E 25710.1 29024.2 103538.7−22.930572 1.00000 1.2467e−116 N 0.248314 0.280322 I E 18320.0 21510.1141124.2 −23.626283 1.00000 1.1296e−123 N 0.129815 0.152420 I H 19655.023276.8 135724.2 −26.080376 1.00000 3.3441e−150 N 0.144816 0.171501 L H45000.3 51092.6 272207.2 −29.904831 1.00000 9.1633e−197 N 0.1653160.187697 A H 52051.2 58421.3 249208.6 −30.120751 1.00000 1.3919e−199 N0.208866 0.234427 G E 8765.5 11960.8 69614.7 −32.104668 1.000002.2298e−226 N 0.125914 0.171814 L E 20637.7 25409.3 157007.0 −32.6965401.00000 9.7828e−235 N 0.131444 0.161835 V H 21098.2 25866.6 140167.6−32.832062 1.00000 1.1500e−236 N 0.150521 0.184540 M C 16433.8 20329.460211.0 −33.571201 1.00000 2.5524e−247 N 0.272937 0.337636 V C 33470.739146.4 134145.5 −34.088036 1.00000 6.1460e−255 N 0.249510 0.291820 V E26733.1 32838.8 197868.3 −36.893349 1.00000 3.3022e−298 N 0.1351060.165963 A E 10155.7 14278.8 89436.9 −37.640052 1.00000 0.0000e+00 N0.113552 0.159652 G H 13372.0 17828.1 78310.4 −37.975062 1.000000.0000e+00 N 0.170756 0.227659 S C 79747.1 88923.2 239515.9 −38.8075981.00000 0.0000e+00 N 0.332951 0.371262 H C 30625.2 38464.2 98652.4−51.171809 1.00000 0.0000e+00 N 0.310435 0.389896 A C 50800.4 63066.5189640.9 −59.786078 1.00000 0.0000e+00 N 0.267877 0.332557 G C 105444.1123958.6 348901.2 −65.492096 1.00000 0.0000e+00 N 0.302218 0.355283

TABLE 5 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityLP CC 3644.5 2731.7 19983.1 18.795754 4.9663e−79 1.00000 N 0.1823790.136702 GY CC 1961.0 1370.5 8928.0 17.337729 1.5760e−67 1.00000 N0.219646 0.153503 PN CC 2684.8 2018.2 10016.5 16.605426 3.9173e−621.00000 N 0.268038 0.201486 GK CH 497.2 251.2 2101.1 16.5398791.6538e−61 1.00000 N 0.236638 0.119564 DG CC 5443.5 4486.7 22101.716.001152 7.1729e−58 1.00000 N 0.246293 0.203000 PG CC 5008.5 4096.220210.3 15.962799 1.3350e−57 1.00000 N 0.247819 0.202681 GF CC 1762.81246.3 9499.7 15.696619 1.0133e−55 1.00000 N 0.185564 0.131193 NG CC4061.8 3269.8 16386.4 15.481858 2.6772e−54 1.00000 N 0.247876 0.199541YP CC 1468.8 1031.4 7236.3 14.706553 3.7500e−49 1.00000 N 0.2029770.142537 FP CC 1415.6 1047.9 8539.3 12.127760 4.6029e−34 1.00000 N0.165775 0.122713 FG HC 520.5 323.3 2395.3 11.793909 2.9912e−32 1.00000N 0.217301 0.134962 PF CC 1170.4 855.8 6117.8 11.594115 2.7366e−311.00000 N 0.191311 0.139893 PE HH 2240.3 1801.5 9246.3 11.5226455.9070e−31 1.00000 N 0.242292 0.194830 TE CH 705.0 481.3 2274.811.486097 1.0424e−30 1.00000 N 0.309917 0.211561 CW HH 58.9 15.3 364.311.413216 8.0109e−30 1.00000 N 0.161680 0.041888 AA HC 564.4 371.62472.5 10.852231 1.3234e−27 1.00000 N 0.228271 0.150281 GI CC 2094.81687.9 12350.9 10.658937 9.1167e−27 1.00000 N 0.169607 0.136663 SA CH566.6 375.7 2576.3 10.654750 1.1178e−26 1.00000 N 0.219928 0.145839 SPCH 805.4 571.9 3849.5 10.583976 2.2515e−26 1.00000 N 0.209222 0.148553AG CC 4357.5 3776.5 21005.1 10.439477 8.9976e−26 1.00000 N 0.2074500.179789 PD CC 3504.6 3007.0 14606.8 10.183074 1.3107e−24 1.00000 N0.239929 0.205862 TG HC 658.1 458.6 2835.1 10.172532 1.7080e−24 1.00000N 0.232126 0.161773 EG EC 541.4 366.0 1983.9 10.152241 2.1774e−241.00000 N 0.272897 0.184487 GL CC 3403.1 2910.1 19636.5 9.9022462.2501e−23 1.00000 N 0.173305 0.148198 KY HC 311.9 189.1 1051.9 9.8561214.8051e−23 1.00000 N 0.296511 0.179808 SG HC 534.7 365.2 2104.2 9.7580781.1308e−22 1.00000 N 0.254111 0.173547 GW CC 570.9 392.3 2987.4 9.6777902.4410e−22 1.00000 N 0.191103 0.131303 WG EC 172.1 86.3 1245.8 9.5789868.3974e−22 1.00000 N 0.138144 0.069246 PD HH 821.7 610.6 3126.7 9.5256281.0190e−21 1.00000 N 0.262801 0.195271 AS HC 387.0 252.5 1734.3 9.1575183.6376e−20 1.00000 N 0.223145 0.145589 SL CH 583.4 412.7 2949.5 9.0624128.1350e−20 1.00000 N 0.197796 0.139911 SF EE 484.7 327.4 4548.1 9.0209551.2109e−19 1.00000 N 0.106572 0.071997 RG HC 457.7 315.6 1580.9 8.9428672.5195e−19 1.00000 N 0.289519 0.199616 DH HC 131.5 66.4 320.4 8.9718562.7193e−19 1.00000 N 0.410424 0.207256 GN CC 3035.8 2625.3 13860.28.899244 3.0996e−19 1.00000 N 0.219030 0.189411 IP CC 1766.5 1451.411589.5 8.843319 5.2673e−19 1.00000 N 0.152422 0.125234 PQ HH 721.3536.6 2873.3 8.841693 5.8387e−19 1.00000 N 0.251035 0.186753 WC CC 77.230.3 378.1 8.889715 7.1536e−19 1.00000 N 0.204179 0.080088 RH HC 196.1112.6 557.9 8.813158 9.7271e−19 1.00000 N 0.351497 0.201757 FS EE 472.3320.3 4887.3 8.783719 1.0221e−18 1.00000 N 0.096638 0.065543 GP CC2507.2 2140.1 12837.1 8.692764 1.9628e−18 1.00000 N 0.195309 0.166713 HPCC 1325.0 1066.2 6355.9 8.687762 2.1421e−18 1.00000 N 0.208468 0.167751PY CC 1128.9 891.7 5689.8 8.651118 2.9912e−18 1.00000 N 0.1984080.156714 ER HC 439.9 308.0 1352.8 8.554820 7.8140e−18 1.00000 N 0.3251770.227648 TN CC 1752.7 1460.3 7607.1 8.511975 9.6926e−18 1.00000 N0.230403 0.191966 HP CH 402.9 273.6 1780.6 8.500886 1.2479e−17 1.00000 N0.226272 0.153628 YS CC 1057.0 832.5 5270.8 8.480789 1.3152e−17 1.00000N 0.200539 0.157938 VG EC 490.3 341.1 4028.2 8.443476 1.9615e−17 1.00000N 0.121717 0.084679 CH CC 252.4 156.4 1105.1 8.287375 8.3120e−17 1.00000N 0.228396 0.141505 GS CE 476.8 337.3 2322.9 8.216422 1.3394e−16 1.00000N 0.205261 0.145201 EH HC 228.4 141.7 666.7 8.208490 1.6592e−16 1.00000N 0.342583 0.212529 PH CC 1015.5 807.7 4323.2 8.108741 3.0021e−161.00000 N 0.234895 0.186827 GF CE 273.1 171.4 2043.3 8.118336 3.2802e−161.00000 N 0.133656 0.083872 EN HC 457.8 327.9 1515.0 8.107234 3.3452e−161.00000 N 0.302178 0.216406 GQ CE 454.4 324.1 1751.3 8.019975 6.7904e−161.00000 N 0.259464 0.185043 CG CH 66.5 26.7 303.6 8.076594 7.6058e−161.00000 N 0.219038 0.087834 QY CC 531.1 389.0 2107.2 7.978552 9.2897e−161.00000 N 0.252041 0.184607 GT EE 527.6 380.8 3779.5 7.930985 1.3508e−151.00000 N 0.139595 0.100763 LG HC 956.8 758.9 5143.0 7.782279 4.1596e−151.00000 N 0.186039 0.147553 RY HC 179.4 105.7 690.9 7.786927 5.2074e−151.00000 N 0.259661 0.153012 CG CC 673.3 510.2 3816.1 7.756211 5.2757e−151.00000 N 0.176437 0.133705 NF HC 110.1 55.6 503.5 7.750356 8.0006e−151.00000 N 0.218669 0.110418 TS CH 275.6 181.2 1047.3 7.710340 8.6337e−151.00000 N 0.263153 0.173029 SV EE 859.1 668.2 9428.4 7.661490 1.0742e−141.00000 N 0.091118 0.070871 KH HC 254.7 167.1 760.9 7.669848 1.2101e−141.00000 N 0.334735 0.219625 SY CC 947.1 755.4 4608.1 7.627352 1.3977e−141.00000 N 0.205529 0.163932 RF HC 157.1 89.5 702.0 7.654627 1.5033e−141.00000 N 0.223789 0.127447 TP CH 756.7 588.2 3562.8 7.601796 1.7380e−141.00000 N 0.212389 0.165105 AG HC 665.7 508.3 3275.0 7.597643 1.8163e−141.00000 N 0.203267 0.155195 QG HC 302.1 204.5 1062.1 7.595025 2.0764e−141.00000 N 0.284436 0.192546 EF HC 151.8 86.1 660.5 7.589196 2.5096e−141.00000 N 0.229826 0.130390 GV CC 2697.8 2362.0 16253.8 7.4739084.2358e−14 1.00000 N 0.165980 0.145319 SR CH 430.0 312.0 1576.3 7.4580815.5765e−14 1.00000 N 0.272791 0.197943 YH HH 259.5 168.6 1432.6 7.4573806.0182e−14 1.00000 N 0.181139 0.117657 HH HH 291.1 195.1 1319.4 7.4499296.2606e−14 1.00000 N 0.220631 0.147834 SE CH 719.8 563.0 2748.7 7.4117617.4454e−14 1.00000 N 0.261869 0.204817 SG EE 554.8 413.5 3653.5 7.3811919.5407e−14 1.00000 N 0.151854 0.113168 HH HC 98.4 50.9 263.6 7.4064671.1640e−13 1.00000 N 0.373293 0.193191 ES EE 396.4 281.8 2060.3 7.3492391.2662e−13 1.00000 N 0.192399 0.136766 QY HC 142.8 81.9 492.7 7.3725731.3154e−13 1.00000 N 0.289832 0.166190 WP CC 391.6 276.7 2395.3 7.3421601.3337e−13 1.00000 N 0.163487 0.115532 EN EC 274.9 184.8 998.5 7.3392521.4549e−13 1.00000 N 0.275313 0.185106 NN CC 1908.0 1644.3 7974.17.300124 1.5931e−13 1.00000 N 0.239275 0.206200 CH HH 134.2 74.4 694.97.336557 1.7294e−13 1.00000 N 0.193121 0.107068 SR HC 280.3 190.0 982.77.294196 2.0261e−13 1.00000 N 0.285235 0.193343 SN HC 268.1 180.3 936.37.276429 2.3278e−13 1.00000 N 0.286340 0.192571 SQ CH 310.6 214.4 1180.77.259299 2.5698e−13 1.00000 N 0.263064 0.181616 SL HC 336.2 232.8 1884.97.239376 2.9156e−13 1.00000 N 0.178365 0.123503 YQ EC 128.8 71.9 489.27.264749 2.9907e−13 1.00000 N 0.263287 0.146984 NH CE 115.1 61.8 505.67.245883 3.5376e−13 1.00000 N 0.227650 0.122134 PA CH 367.6 262.5 1530.77.128794 6.4728e−13 1.00000 N 0.240152 0.171473 GE CE 635.3 493.6 2532.67.109712 6.9708e−13 1.00000 N 0.250849 0.194887 TG CC 3208.1 2864.216191.1 7.082544 7.6223e−13 1.00000 N 0.198140 0.176900 QF HC 113.5 61.6439.7 7.122281 8.7171e−13 1.00000 N 0.258131 0.140203 NY HC 149.3 88.3580.0 7.051042 1.3429e−12 1.00000 N 0.257414 0.152234 FT EE 494.0 365.05183.9 7.003659 1.5130e−12 1.00000 N 0.095295 0.070409 QS EE 288.5 196.31661.4 7.008085 1.5838e−12 1.00000 N 0.173649 0.118151 YN HC 175.1 108.8647.7 6.965652 2.3708e−12 1.00000 N 0.270341 0.168011 RN HC 291.3 203.2970.0 6.948606 2.4377e−12 1.00000 N 0.300309 0.209514

TABLE 6 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySxE ChH 1700.4 969.9 6349.9 25.481565 2.4624e−143 1.00000 N 0.2677840.152747 TxE ChH 1585.3 930.3 5513.1 23.554174 8.6926e−123 1.00000 N0.287551 0.168742 SxA ChH 850.1 421.1 3347.3 22.357026 9.2441e−1111.00000 N 0.253966 0.125812 DxA ChH 999.6 535.7 3592.5 21.7314018.6234e−105 1.00000 N 0.278246 0.149103 TxA ChH 715.6 354.6 2588.820.639026 1.1060e−94 1.00000 N 0.276422 0.136960 AxG HcC 1022.2 597.74368.0 18.691902 4.3518e−78 1.00000 N 0.234020 0.136825 NxA ChH 528.3260.2 2030.4 17.797648 6.6617e−71 1.00000 N 0.260195 0.128165 DxS ChH748.1 418.8 2698.0 17.510347 9.5251e−69 1.00000 N 0.277279 0.155210 NxEChH 840.2 510.2 3189.6 15.940329 2.4469e−57 1.00000 N 0.263419 0.159957DxR ChH 544.4 295.2 1961.9 15.736436 7.0040e−56 1.00000 N 0.2774860.150465 SxS ChH 515.9 277.0 2080.1 15.419244 1.0009e−53 1.00000 N0.248017 0.133156 SxQ ChH 428.7 217.8 1547.0 15.412393 1.1886e−531.00000 N 0.277117 0.140817 DxS CcC 2391.5 1816.6 11758.1 14.6701906.0377e−49 1.00000 N 0.203392 0.154495 RxE EeE 590.6 340.3 2432.214.631398 1.3602e−48 1.00000 N 0.242825 0.139910 DxR CcC 1514.3 1076.26808.8 14.555462 3.4368e−48 1.00000 N 0.222403 0.158055 PxE ChH 750.1466.0 2940.0 14.345884 8.1316e−47 1.00000 N 0.255136 0.158508 DxE ChH1054.1 710.5 4231.1 14.129521 1.6724e−45 1.00000 N 0.249131 0.167933 RxEChH 511.7 293.9 1726.9 13.949854 2.4681e−44 1.00000 N 0.296311 0.170167TxY EeE 525.3 300.0 3697.0 13.569099 4.6027e−42 1.00000 N 0.1420880.081150 SxG HcC 511.7 296.4 2101.8 13.496246 1.2581e−41 1.00000 N0.243458 0.141004 DxD ChH 676.9 423.4 2579.0 13.477926 1.5116e−411.00000 N 0.262466 0.164158 TxQ ChH 358.8 189.9 1213.7 13.3473421.0422e−40 1.00000 N 0.295625 0.156445 KxG HhC 794.3 518.5 3293.513.196235 6.3329e−40 1.00000 N 0.241172 0.157426 ExG HcC 907.8 610.73653.9 13.173395 8.3719e−40 1.00000 N 0.248447 0.167137 YxG EcC 388.8209.7 2305.9 12.974743 1.3641e−38 1.00000 N 0.168611 0.090928 SxD ChH668.8 424.4 2701.0 12.924936 2.2948e−38 1.00000 N 0.247612 0.157111 DxQChH 411.3 232.6 1454.6 12.781923 1.6375e−37 1.00000 N 0.282758 0.159919ExG HhC 887.1 600.4 3922.9 12.716402 3.1827e−37 1.00000 N 0.2261340.153038 AxG HhC 719.4 465.5 3596.3 12.614343 1.2059e−36 1.00000 N0.200039 0.129430 KxG HcC 815.5 546.9 3223.8 12.605467 1.3261e−361.00000 N 0.252962 0.169638 SxW ChH 89.6 27.5 434.3 12.254000 2.6846e−341.00000 N 0.206309 0.063216 VxC EcC 60.4 14.6 326.9 12.283869 2.8734e−341.00000 N 0.184766 0.044568 TxD ChH 596.6 380.9 2366.4 12.0653911.1295e−33 1.00000 N 0.252113 0.160964 QxG HcC 492.4 302.3 1853.511.951463 4.6538e−33 1.00000 N 0.265660 0.163098 RxG HcC 600.4 385.32430.5 11.946166 4.7458e−33 1.00000 N 0.247027 0.158526 LxP CcH 462.1275.0 3282.8 11.786533 3.3267e−32 1.00000 N 0.140764 0.083772 PxD ChH394.7 232.9 1487.4 11.547933 5.7222e−31 1.00000 N 0.265362 0.156556 DxNChH 418.4 250.6 1597.8 11.545587 5.7935e−31 1.00000 N 0.261860 0.156827PxS ChH 359.8 206.0 1492.8 11.543336 6.1661e−31 1.00000 N 0.2410240.137984 NxR ChH 288.4 155.7 1067.1 11.503618 1.0444e−30 1.00000 N0.270265 0.145939 SxR ChH 317.2 175.7 1335.1 11.460734 1.6564e−301.00000 N 0.237585 0.131564 GxC CcH 44.3 9.7 152.7 11.437654 9.0069e−301.00000 N 0.290111 0.063838 SxY ChH 163.2 72.1 829.5 11.2206693.2336e−29 1.00000 N 0.196745 0.086964 QxF EeE 222.0 109.4 1489.411.185189 4.2124e−29 1.00000 N 0.149053 0.073447 GxT ChH 279.3 149.21676.8 11.158528 5.2645e−29 1.00000 N 0.166567 0.088982 NxD ChH 495.1313.9 2040.0 11.121331 6.9636e−29 1.00000 N 0.242696 0.153854 NxQ ChH274.2 149.6 988.7 11.058345 1.6363e−28 1.00000 N 0.277334 0.151307 NxNChH 250.9 133.3 909.1 11.031095 2.2760e−28 1.00000 N 0.275987 0.146586QxI EeE 286.5 155.2 2264.8 10.922487 7.1076e−28 1.00000 N 0.1265010.068519 RxD ChH 290.3 164.7 1023.0 10.679839 9.9908e−27 1.00000 N0.283773 0.161040 RxG HhC 536.7 352.1 2365.3 10.663828 1.0247e−261.00000 N 0.226906 0.148858 RxY EeE 321.4 183.3 2132.7 10.6663161.1077e−26 1.00000 N 0.150701 0.085960 PxN ChH 192.2 95.7 703.210.613987 2.3079e−26 1.00000 N 0.273322 0.136083 GxP CcC 2805.0 2335.417106.8 10.456739 7.6737e−26 1.00000 N 0.163970 0.136520 SxT ChH 257.9141.7 1197.1 10.391203 2.1709e−25 1.00000 N 0.215437 0.118404 QxN EeC209.1 109.1 732.3 10.376889 2.7159e−25 1.00000 N 0.285539 0.148994 DxYEeE 220.1 114.3 1491.6 10.296246 6.0672e−25 1.00000 N 0.147560 0.076640SxN ChH 239.0 129.9 996.5 10.263686 8.3511e−25 1.00000 N 0.2398390.130365 DxG HcC 432.5 277.7 1780.1 10.113180 3.3685e−24 1.00000 N0.242964 0.155990 YxY EeE 228.8 121.2 2218.0 10.058017 6.7978e−241.00000 N 0.103156 0.054624 NxQ CcC 892.6 658.1 4118.3 9.9726481.2435e−23 1.00000 N 0.216740 0.159798 ExR EeE 515.0 343.7 2444.09.970753 1.3711e−23 1.00000 N 0.210720 0.140610 GxT CcE 939.2 694.35432.7 9.951870 1.5175e−23 1.00000 N 0.172879 0.127800 GxV CcE 809.8580.9 6541.4 9.949285 1.5796e−23 1.00000 N 0.123796 0.088803 NxY CcE207.7 110.3 1062.5 9.790792 1.0127e−22 1.00000 N 0.195482 0.103850 PxYCcC 713.9 507.6 4347.2 9.740513 1.2772e−22 1.00000 N 0.164221 0.116776AxP HcC 365.8 228.9 1699.7 9.723656 1.6933e−22 1.00000 N 0.2152140.134695 ExF EeE 256.9 144.6 1850.1 9.723236 1.8348e−22 1.00000 N0.138857 0.078174 QxG HhC 389.7 248.6 1652.1 9.705388 2.0025e−22 1.00000N 0.235882 0.150503 TxS ChH 302.5 183.7 1336.5 9.440319 2.7128e−211.00000 N 0.226337 0.137430 TxV EeE 635.9 444.3 7269.4 9.3820324.0803e−21 1.00000 N 0.087476 0.061117 PxA ChH 300.2 182.7 1377.99.335371 7.3154e−21 1.00000 N 0.217868 0.132582 SxG HhC 349.5 220.31705.1 9.325761 7.7389e−21 1.00000 N 0.204973 0.129216 ExR CeE 196.5108.0 664.3 9.299003 1.1605e−20 1.00000 N 0.295800 0.162652 QxY EeE187.6 98.9 1255.4 9.293234 1.2227e−20 1.00000 N 0.149434 0.078777 GxRCcE 762.1 561.9 3614.7 9.192475 2.3756e−20 1.00000 N 0.210834 0.155436DxR HcC 120.8 57.1 342.9 9.241439 2.3884e−20 1.00000 N 0.352289 0.166413LxA CcH 231.9 130.5 1826.3 9.214022 2.3961e−20 1.00000 N 0.1269780.071445 DxG HhC 361.9 232.4 1588.1 9.195611 2.5922e−20 1.00000 N0.227882 0.146327 CxP ChH 38.6 10.0 195.9 9.318972 2.6851e−20 1.00000 N0.197039 0.050815 YxY CcE 84.9 33.4 504.5 9.207153 3.8374e−20 1.00000 N0.168285 0.066298 NxS ChH 286.4 174.8 1258.8 9.101010 6.5075e−20 1.00000N 0.227518 0.138825 RxP HcC 272.6 165.4 1046.7 9.080465 7.9710e−201.00000 N 0.260438 0.158052 DxT ChH 325.9 205.3 1490.9 9.0643518.8406e−20 1.00000 N 0.218593 0.137700 TxK ChH 363.6 237.5 1518.28.909320 3.5284e−19 1.00000 N 0.239494 0.156432 DxN CcC 1643.8 1344.48702.1 8.880344 3.8076e−19 1.00000 N 0.188897 0.154491 GxC EcH 23.6 2.059.1 15.334095 4.9477e−19 1.00000 B 0.399323 0.034629 WxG CcH 47.8 14.9153.6 8.967722 5.1676e−19 1.00000 N 0.311198 0.097025 RxF EeE 260.1154.0 2165.0 8.868217 5.4042e−19 1.00000 N 0.120139 0.071144 NxQ CcE241.5 143.8 921.8 8.867344 5.6237e−19 1.00000 N 0.261987 0.156009 NxGHcC 306.9 192.6 1423.3 8.859907 5.6640e−19 1.00000 N 0.215626 0.135299NxG EcC 266.8 161.1 1531.2 8.808720 9.1688e−19 1.00000 N 0.1742420.105181 DxY ChH 151.5 78.1 697.2 8.818579 9.8907e−19 1.00000 N 0.2172980.111980 DxR EeE 241.4 143.3 1105.4 8.782154 1.1928e−18 1.00000 N0.218382 0.129651 GxW CcE 181.9 98.7 1119.5 8.764418 1.4965e−18 1.00000N 0.162483 0.088199 YxE EeE 316.8 199.4 2122.7 8.730258 1.7640e−181.00000 N 0.149244 0.093957 SxN HcC 189.6 106.4 732.9 8.7177042.2519e−18 1.00000 N 0.258698 0.145238 VxK CcH 158.9 83.0 1054.78.679088 3.2923e−18 1.00000 N 0.150659 0.078699 ExR HcC 208.6 122.8704.9 8.523866 1.1834e−17 1.00000 N 0.295929 0.174169

TABLE 7 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityVGK CCH 77.0 7.3 333.8 26.010341 2.4051e−147 1.00000 N 0.230677 0.021974GKT CHH 153.4 31.1 637.2 22.460983 3.9337e−111 1.00000 N 0.2407410.048882 AGK CCH 62.8 6.9 203.7 21.675549 1.1541e−102 1.00000 N 0.3082970.033809 GKS CHH 109.3 20.3 431.2 20.202696 4.5922e−90 1.00000 N0.253479 0.047186 SGK CCH 62.0 8.1 285.5 19.164056 1.1096e−80 1.00000 N0.217163 0.028485 TGK CCH 58.3 9.7 201.6 15.993902 9.7605e−57 1.00000 N0.289187 0.048116 SCW CHH 23.8 0.1 62.0 65.127700 4.1919e−46 1.00000 B0.383871 0.002135 KTT HHH 82.7 23.0 432.3 12.788449 3.7526e−37 1.00000 N0.191302 0.053227 GLG CHH 32.3 5.5 150.3 11.613338 2.1761e−30 1.00000 N0.214904 0.036728 VAC ECC 35.5 3.0 69.4 19.303678 1.0904e−29 1.00000 B0.511527 0.042754 ACK CCC 43.1 9.6 105.9 11.302265 4.3157e−29 1.00000 N0.406988 0.091043 STK CEE 101.6 38.9 261.2 10.906198 1.3949e−27 1.00000N 0.388974 0.148807 NVA EEC 38.6 8.4 107.2 10.808062 1.0942e−26 1.00000N 0.360075 0.078810 SWG EEC 39.0 8.5 240.0 10.655127 5.3105e−26 1.00000N 0.162500 0.035402 LCT CCC 29.6 5.8 90.5 10.256670 5.0074e−24 1.00000 N0.327072 0.063723 CKN CCC 43.3 11.3 142.4 9.894711 1.0185e−22 1.00000 N0.304073 0.079616 AAG HCC 163.7 81.2 702.7 9.726602 2.0695e−22 1.00000 N0.232959 0.115625 TEA CHH 96.0 39.7 292.4 9.607131 8.5115e−22 1.00000 N0.328317 0.135830 SAA CHH 97.7 40.5 376.8 9.504205 2.2325e−21 1.00000 N0.259289 0.107580 ACW CHH 7.1 0.0 7.0 66.349669 2.5416e−20 1.00000 B1.014286 0.001588 TNS HHH 28.8 6.4 113.7 9.149010 1.8584e−19 1.00000 N0.253298 0.056008 GLP CCC 279.5 169.6 1833.1 8.854745 6.0139e−19 1.00000N 0.152474 0.092541 NIF CHH 25.6 5.4 79.2 9.005026 8.0205e−19 1.00000 N0.323232 0.068183 SIP CCC 122.5 58.7 674.0 8.717895 2.5843e−18 1.00000 N0.181751 0.087074 WCG CCH 28.7 4.0 56.9 12.768736 3.8448e−18 1.00000 B0.504394 0.070649 FPG CCC 138.7 69.5 857.5 8.665190 3.8961e−18 1.00000 N0.161749 0.081010 GFT CCH 31.4 8.1 73.3 8.717496 7.2684e−18 1.00000 N0.428377 0.109906 FTN CHH 29.5 7.6 58.8 8.553956 3.1605e−17 1.00000 N0.501701 0.128453 QFN CEC 25.0 3.5 41.7 12.091685 4.5918e−17 1.00000 B0.599520 0.082983 PGP CCC 141.6 73.8 708.1 8.346900 5.8862e−17 1.00000 N0.199972 0.104156 CSA CCC 35.9 10.0 203.2 8.423091 7.2418e−17 1.00000 N0.176673 0.049053 NHG CEE 10.8 0.2 15.3 24.175566 8.8421e−17 1.00000 B0.705882 0.012739 PTW CEE 16.2 1.1 23.2 14.652981 1.4058e−16 1.00000 B0.698276 0.047995 SRW CHH 21.5 2.1 52.8 13.577010 2.1455e−16 1.00000 B0.407197 0.040196 MDS ECC 25.5 3.2 83.9 12.774800 2.5660e−16 1.00000 B0.303933 0.037835 STM CCE 24.9 3.3 57.0 12.327304 3.1613e−16 1.00000 B0.436842 0.057314 CGP CHH 24.5 3.1 61.6 12.501422 4.2984e−16 1.00000 B0.397727 0.050135 AGP CCC 129.7 67.0 642.9 8.089518 5.0769e−16 1.00000 N0.201742 0.104248 GSC CCH 17.4 1.2 46.8 14.920627 7.5249e−16 1.00000 B0.371795 0.025829 TKV EEE 147.9 80.2 815.1 7.963248 1.3456e−15 1.00000 N0.181450 0.098379 TVA CHH 40.3 13.0 137.0 7.949197 3.0102e−15 1.00000 N0.294161 0.095013 QGQ CCC 91.8 43.4 358.4 7.828759 4.6739e−15 1.00000 N0.256138 0.121185 SVT EEE 97.7 46.7 1097.2 7.630634 2.0807e−14 1.00000 N0.089045 0.042549 YPS CCC 75.2 33.3 377.0 7.598203 3.0137e−14 1.00000 N0.199469 0.088388 LSA CCH 54.0 20.6 304.8 7.618303 3.0894e−14 1.00000 N0.177165 0.067607 TPG CCC 165.0 95.3 927.3 7.542830 3.4767e−14 1.00000 N0.177936 0.102732 GSC ECH 11.5 0.4 30.6 17.936056 4.0165e−14 1.00000 B0.375817 0.012703 KVD EEE 140.3 78.3 634.6 7.478628 5.9323e−14 1.00000 N0.221084 0.123433 VNG ECC 97.3 47.6 641.0 7.485467 6.3078e−14 1.00000 N0.151794 0.074270 NHA CEE 13.1 0.7 39.4 15.069522 8.1696e−14 1.00000 B0.332487 0.017519 DAC ECC 11.1 0.4 76.4 17.855983 1.1616e−13 1.00000 B0.145288 0.004755 PTE CCH 41.7 14.5 177.9 7.447010 1.3352e−13 1.00000 N0.234401 0.081576 VNT EEE 23.7 5.8 202.1 7.516216 1.3762e−13 1.00000 N0.117269 0.028818 QRG HCC 49.4 19.2 147.2 7.401983 1.6748e−13 1.00000 N0.335598 0.130253 DRC CCC 32.2 9.8 128.7 7.444459 1.6904e−13 1.00000 N0.250194 0.076146 TPN CHH 40.3 14.1 123.0 7.419598 1.6934e−13 1.00000 N0.327642 0.114566 QSP EEC 55.5 22.0 358.1 7.386743 1.7114e−13 1.00000 N0.154985 0.061328 NPT CCC 103.0 52.3 577.1 7.347429 1.7329e−13 1.00000 N0.178479 0.090661 PGA CCC 212.4 132.7 1275.2 7.304192 1.9593e−13 1.00000N 0.166562 0.104098 TMS CEE 18.0 1.9 61.6 11.976454 2.1832e−13 1.00000 B0.292208 0.030366 WNI ECC 14.3 1.7 14.6 10.368372 2.5065e−13 1.00000 B0.979452 0.114714 SLP CCC 173.3 103.4 1051.9 7.242306 3.2273e−13 1.00000N 0.164750 0.098276 VWG CCC 27.0 7.6 100.7 7.352114 3.9459e−13 1.00000 N0.268123 0.075068 YAS HHC 21.3 5.1 83.8 7.373798 4.4718e−13 1.00000 N0.254177 0.061159 ETG HHC 74.9 34.7 331.4 7.207961 5.4644e−13 1.00000 N0.226011 0.104757 DGR CCC 235.9 153.2 1180.8 7.159780 5.5359e−13 1.00000N 0.199780 0.129763 PGD CCC 199.2 124.2 1125.9 7.138468 6.6622e−131.00000 N 0.176925 0.110285 KYG HHC 97.9 50.3 426.2 7.139373 8.0699e−131.00000 N 0.229704 0.118099 PNR HHH 26.3 7.4 104.2 7.227147 9.8791e−131.00000 N 0.252399 0.070802 YRG ECC 44.6 16.9 163.1 7.137134 1.2043e−121.00000 N 0.273452 0.103338 LPP CCH 51.0 20.2 286.8 7.109054 1.3390e−121.00000 N 0.177824 0.070421 ALG HHC 97.2 49.6 629.4 7.045039 1.5728e−121.00000 N 0.154433 0.078782 LPP CCC 180.4 110.2 1229.1 7.0149721.6415e−12 1.00000 N 0.146774 0.089620 VPG CCC 166.4 99.6 1134.47.006024 1.7808e−12 1.00000 N 0.146685 0.087813 GLN CCC 129.0 72.3 760.87.013456 1.8054e−12 1.00000 N 0.169558 0.095002 DGS CCC 313.8 217.41868.1 6.955249 2.2714e−12 1.00000 N 0.167978 0.116375 TQA CHH 28.7 8.879.5 7.084686 2.4870e−12 1.00000 N 0.361006 0.111203 LGF HCC 32.9 10.6200.8 7.063506 2.5027e−12 1.00000 N 0.163845 0.052585 VGS ECC 50.8 20.2338.6 7.014581 2.6019e−12 1.00000 N 0.150030 0.059706 VGG ECC 71.2 32.4623.7 6.989302 2.6159e−12 1.00000 N 0.114157 0.052013 DAG HCC 85.4 43.1354.4 6.866307 5.8013e−12 1.00000 N 0.240971 0.121717 NFQ CCC 43.0 16.4179.3 6.908802 6.0451e−12 1.00000 N 0.239822 0.091247 PLP CCC 188.1117.9 1190.8 6.815600 6.5703e−12 1.00000 N 0.157961 0.098979 GVG CCC153.3 91.0 1178.1 6.798433 7.7111e−12 1.00000 N 0.130125 0.077244 KSTHHH 55.7 23.6 352.4 6.836180 8.5034e−12 1.00000 N 0.158059 0.067006 GVCCHH 11.0 0.6 29.2 13.353406 1.0076e−11 1.00000 B 0.376712 0.021150 LNHCCE 18.5 2.6 48.2 10.211731 1.1142e−11 1.00000 B 0.383817 0.053329 FNTECC 25.2 5.0 90.3 9.300990 1.1273e−11 1.00000 B 0.279070 0.055319 AFGHHC 43.0 16.4 221.9 6.811870 1.1651e−11 1.00000 N 0.193781 0.074044 YDYCCE 24.7 7.0 113.0 6.871379 1.2210e−11 1.00000 N 0.218584 0.062322 EFGHHC 47.2 19.1 189.4 6.788653 1.2971e−11 1.00000 N 0.249208 0.100739 GADCCC 214.2 138.8 1524.5 6.711627 1.3044e−11 1.00000 N 0.140505 0.091053PGY CCC 82.9 41.6 425.5 6.738554 1.3978e−11 1.00000 N 0.194830 0.097795VSG ECC 37.7 13.5 238.1 6.793587 1.4324e−11 1.00000 N 0.158337 0.056600VPS CHH 23.5 6.7 71.3 6.843087 1.5709e−11 1.00000 N 0.329593 0.093573NTK CEE 60.7 27.9 192.9 6.723444 1.7833e−11 1.00000 N 0.314671 0.144478KEG HHC 69.4 33.3 254.1 6.699047 1.9722e−11 1.00000 N 0.273121 0.131224ERG HCC 94.3 50.4 359.7 6.658952 2.3048e−11 1.00000 N 0.262163 0.140245TGN CCH 20.5 3.8 35.3 8.996500 2.3578e−11 1.00000 B 0.580737 0.108948

TABLE 8 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityExxR HhhH 4348.2 2217.2 15346.0 48.929948 0.0000e+00 1.00000 N 0.2833440.144479 DxxR HhhH 1950.8 1065.5 7576.4 29.254482 3.1941e−188 1.00000 N0.257484 0.140641 AxxR HhhH 1961.9 1175.2 11570.1 24.209128 1.2946e−1291.00000 N 0.169566 0.101576 QxxR HhhH 1231.2 658.8 5042.5 23.9153821.7473e−126 1.00000 N 0.244165 0.130659 RxxE HhhH 2176.8 1363.9 9113.523.870272 4.4302e−126 1.00000 N 0.238854 0.149656 SxxE ChhH 1232.3 662.15215.8 23.715081 2.0648e−124 1.00000 N 0.236263 0.126945 TxxE ChhH1201.2 669.0 5025.4 22.099248 2.5443e−108 1.00000 N 0.239026 0.133125RxxR HhhH 1439.9 849.7 5869.7 21.892063 2.3219e−106 1.00000 N 0.2453110.144767 NxxR HhhH 887.4 483.2 3933.1 19.632154 6.6235e−86 1.00000 N0.225624 0.122860 ExxL HhhH 2067.7 1372.8 16331.3 19.596830 1.0853e−851.00000 N 0.126610 0.084059 ExxE HhhH 2778.6 2009.6 13291.7 18.6185281.4251e−77 1.00000 N 0.209048 0.151195 RxxQ HhhH 1120.7 683.5 5021.117.993739 1.5808e−72 1.00000 N 0.223198 0.136120 AxxA HhhH 1938.9 1310.022725.8 17.898378 7.8366e−72 1.00000 N 0.085317 0.057645 LxxQ HhhH1044.9 618.7 8365.8 17.803559 4.8141e−71 1.00000 N 0.124901 0.073960TxxQ ChhH 610.7 320.4 2537.9 17.349010 1.6872e−67 1.00000 N 0.2406320.126252 LxxE HhhH 1464.3 953.5 12363.8 17.217744 1.3074e−66 1.00000 N0.118434 0.077123 SxxR HhhH 897.4 526.5 4584.1 17.180436 2.7728e−661.00000 N 0.195764 0.114856 PxxR HhhH 724.7 403.3 3049.0 17.1799592.9726e−66 1.00000 N 0.237684 0.132276 ExxK HhhH 3386.2 2586.3 16930.717.087679 1.1008e−65 1.00000 N 0.200004 0.152759 ExxG HhhC 927.7 556.23737.1 17.076826 1.6364e−65 1.00000 N 0.248241 0.148819 NxxE ChhH 661.0364.0 2655.9 16.758653 3.9327e−63 1.00000 N 0.248880 0.137048 AxxG HhhC719.2 401.9 3735.5 16.753239 4.1779e−63 1.00000 N 0.192531 0.107594 ExxHHhhH 621.9 333.5 3030.1 16.736834 5.7488e−63 1.00000 N 0.205241 0.110077ExxA HhhH 2290.7 1653.8 15597.0 16.562861 8.0240e−62 1.00000 N 0.1468680.106036 QxxE HhhH 1402.9 938.5 6562.3 16.375826 1.9012e−60 1.00000 N0.213782 0.143012 AxxQ HhhH 1213.0 780.1 7792.0 16.340013 3.4909e−601.00000 N 0.155672 0.100112 QxxQ HhhH 966.0 596.4 4465.5 16.2565371.4369e−59 1.00000 N 0.216325 0.133567 SxxQ ChhH 506.0 259.3 2528.016.170844 6.8893e−59 1.00000 N 0.200158 0.102577 QxxA HhhH 1224.8 792.58547.3 16.121839 1.2114e−58 1.00000 N 0.143297 0.092719 AxxE HhhH 1984.01414.1 13871.3 15.991423 9.1835e−58 1.00000 N 0.143029 0.101946 ExxNHhhH 1108.5 713.4 5126.3 15.942068 2.2333e−57 1.00000 N 0.2162380.139170 QxxL HhhH 1100.1 695.9 9726.7 15.900088 4.3300e−57 1.00000 N0.113101 0.071549 QxxK HhhH 1225.8 809.9 5705.9 15.775674 3.0884e−561.00000 N 0.214830 0.141944 KxxG HhhC 867.2 534.5 3433.8 15.6589352.0892e−55 1.00000 N 0.252548 0.155669 NxxQ ChhH 332.0 152.1 1273.815.544051 1.7117e−54 1.00000 N 0.260637 0.119410 SxxQ HhhH 668.9 384.63261.9 15.434403 7.3145e−54 1.00000 N 0.205065 0.117911 RxxG HhhC 641.9369.4 2583.0 15.313256 4.8017e−53 1.00000 N 0.248509 0.143024 SxxD ChhH740.5 443.0 3728.2 15.055046 2.3442e−51 1.00000 N 0.198621 0.118834 DxxEHhhH 1237.9 835.4 5826.5 15.045687 2.4433e−51 1.00000 N 0.2124600.143381 ExxQ HhhH 1562.3 1108.4 7657.2 14.743542 2.1528e−49 1.00000 N0.204030 0.144748 GxxT ChhH 295.6 132.8 1720.0 14.702270 6.0666e−491.00000 N 0.171860 0.077226 YxxE HhhH 584.6 335.1 3516.7 14.3306781.0637e−46 1.00000 N 0.166235 0.095283 NxxN HhhH 471.7 257.7 2067.414.251900 3.5119e−46 1.00000 N 0.228161 0.124630 ExxR HhhC 380.1 197.91322.8 14.041511 7.4744e−45 1.00000 N 0.287345 0.149630 QxxG HhhC 411.9219.5 1555.2 14.009672 1.1350e−44 1.00000 N 0.264853 0.141160 TxxR HhhH765.0 482.3 4295.0 13.660714 1.2139e−42 1.00000 N 0.178114 0.112300 DxxEChhH 635.3 386.1 2788.7 13.662147 1.2445e−42 1.00000 N 0.227812 0.138458YxxQ HhhH 398.5 209.7 2527.7 13.617674 2.5739e−42 1.00000 N 0.1576530.082949 QxxN HhhH 542.7 316.8 2555.0 13.561238 5.1153e−42 1.00000 N0.212407 0.123988 DxxG HhhC 433.3 241.9 1739.4 13.261160 3.0841e−401.00000 N 0.249109 0.139082 WxxE HhhH 321.8 161.2 1855.3 13.2423534.3211e−40 1.00000 N 0.173449 0.086864 ExxD HhhH 1269.7 909.8 6134.412.929975 1.9255e−38 1.00000 N 0.206980 0.148308 HxxR HhhH 430.4 241.72107.3 12.903646 3.3433e−38 1.00000 N 0.204242 0.114677 DxxL HhhH 1010.9687.7 8629.3 12.846314 5.8301e−38 1.00000 N 0.117147 0.079696 ExxG HhcC744.6 484.9 3281.4 12.775335 1.5440e−37 1.00000 N 0.226915 0.147772 ExxSHhhH 1097.9 768.3 6163.8 12.711229 3.2768e−37 1.00000 N 0.1781210.124641 QxxI HhhH 566.2 340.5 4971.5 12.671523 6.0800e−37 1.00000 N0.113889 0.068494 DxxA ChhH 593.4 365.5 3282.0 12.648212 8.1426e−371.00000 N 0.180804 0.111354 SxxG HhhC 347.9 186.1 1537.7 12.6462009.6469e−37 1.00000 N 0.226247 0.121053 AxxD HhhH 1046.4 726.1 6872.912.566935 2.0561e−36 1.00000 N 0.152250 0.105654 HxxN HhhH 260.9 127.11176.7 12.560981 3.1284e−36 1.00000 N 0.221722 0.108046 DxxQ HhhH 723.6471.1 3555.4 12.487682 5.9445e−36 1.00000 N 0.203521 0.132515 KxxR HhhH1092.2 773.5 5096.1 12.440642 1.0036e−35 1.00000 N 0.214321 0.151790KxxE HhhH 2359.1 1866.8 12050.7 12.393165 1.6647e−35 1.00000 N 0.1957650.154916 ExxY HhhH 594.3 368.6 4092.2 12.321576 4.8612e−35 1.00000 N0.145228 0.090082 DxxS ChhH 389.9 219.1 1996.9 12.233933 1.5902e−341.00000 N 0.195253 0.109696 RxxE ChhH 293.5 153.3 1085.3 12.2199432.0770e−34 1.00000 N 0.270432 0.141246 NxxA HhhH 615.2 385.8 4642.012.194745 2.2966e−34 1.00000 N 0.132529 0.083118 RxxG HhcC 659.6 428.82824.2 12.104920 6.8433e−34 1.00000 N 0.233553 0.151816 NxxD ChhH 392.2223.3 1771.2 12.091210 9.0805e−34 1.00000 N 0.221432 0.126069 DxxQ ChhH408.5 236.2 1714.9 12.072696 1.1263e−33 1.00000 N 0.238206 0.137738 NxxLChhH 281.7 142.8 1993.4 12.058417 1.4819e−33 1.00000 N 0.141316 0.071657HxxE HhhH 473.2 283.5 2266.1 12.043282 1.5453e−33 1.00000 N 0.2088170.125115 GxxE ChhH 439.0 257.5 2293.0 12.008640 2.3858e−33 1.00000 N0.191452 0.112279 NxxQ HhhH 424.5 248.0 2082.1 11.945249 5.1603e−331.00000 N 0.203881 0.119090 PxxQ ChhH 241.0 119.4 891.4 11.9600565.1935e−33 1.00000 N 0.270361 0.133930 DxxI HhhH 616.4 390.7 5172.811.873778 1.1089e−32 1.00000 N 0.119162 0.075536 DxxN HhhH 709.7 470.73574.6 11.821688 2.0234e−32 1.00000 N 0.198540 0.131680 PxxQ HhhH 457.1275.6 2183.2 11.694718 9.9071e−32 1.00000 N 0.209372 0.126244 AxxS HhhH758.2 505.5 6977.1 11.670720 1.1797e−31 1.00000 N 0.108670 0.072450 PxxEChhH 403.9 238.4 1641.8 11.591112 3.4386e−31 1.00000 N 0.246010 0.145223LxxR HhhH 1020.1 722.6 9691.9 11.504616 7.8213e−31 1.00000 N 0.1052530.074557 DxxD ChhH 374.5 215.7 1824.1 11.518567 8.0950e−31 1.00000 N0.205307 0.118228 NxxN ChhH 243.7 123.8 1030.3 11.485674 1.3538e−301.00000 N 0.236533 0.120178 DxxR ChhH 424.4 255.7 1831.5 11.3757354.0622e−30 1.00000 N 0.231723 0.139600 NxxA ChhH 312.9 171.5 1945.511.304387 9.8336e−30 1.00000 N 0.160833 0.088165 YxxR HhhH 419.1 249.32896.8 11.250980 1.6663e−29 1.00000 N 0.144677 0.086053 DxxL ChhH 415.6247.0 2867.7 11.221422 2.3305e−29 1.00000 N 0.144925 0.086134 QxxY HhhH320.8 177.7 2179.5 11.200574 3.1483e−29 1.00000 N 0.147190 0.081535 DxxTChhH 458.9 282.2 2519.2 11.161309 4.4957e−29 1.00000 N 0.182161 0.112025CxxC HhhH 91.2 31.4 345.5 11.183314 7.0327e−29 1.00000 N 0.2639650.090959 PxxL HhhH 608.9 395.6 6143.7 11.089911 9.3855e−29 1.00000 N0.099110 0.064384 DxxY HhhH 368.3 213.9 2333.5 11.075011 1.2369e−281.00000 N 0.157832 0.091673 KxxG HhcC 745.1 514.8 3321.5 11.0410051.5816e−28 1.00000 N 0.224326 0.154995 RxxD HhhH 732.4 503.2 3530.911.036073 1.6724e−28 1.00000 N 0.207426 0.142503 RxxG EecC 324.0 184.11428.3 11.048350 1.7317e−28 1.00000 N 0.226843 0.128887 GxxS ChhH 183.585.6 1241.1 10.968621 5.0167e−28 1.00000 N 0.147853 0.068961 DxxA HhhH1133.7 834.4 8331.6 10.924825 5.3609e−28 1.00000 N 0.136072 0.100143RxxQ ChhH 123.0 50.4 388.2 10.969534 6.1545e−28 1.00000 N 0.3168470.129758

TABLE 9 In Expected P-Value P-Value Observed Null Sequence StructureEpitopes in Epi In PDB Z-Score Upper Lower Distribution RatioProbability GxGK CcCH 167.7 26.9 711.5 27.705426  4.5759e−168 1.00000 N0.235699 0.037747 VxKS CcHH 52.9 6.6 219.9 18.362884 4.9087e−74 1.00000N 0.240564 0.029847 GxTT ChHH 83.7 17.2 346.9 16.454208 2.9941e−601.00000 N 0.241280 0.049554 GxCW CcHH 29.6 0.4 45.0 46.718591 4.9102e−491.00000 B 0.657778 0.008761 VxCK EcCC 42.0 3.1 60.9 22.843225 2.8454e−401.00000 B 0.689655 0.050241 GxCW EcHH 23.1 0.3 37.8 42.803527 1.7396e−391.00000 B 0.611111 0.007573 AxKT CcHH 36.8 2.4 104.5 22.2441251.2660e−32 1.00000 B 0.352153 0.023376 CxNG CcCC 44.4 9.3 177.511.796465 1.4799e−31 1.00000 N 0.250141 0.052558 SxAE ChHH 122.9 48.4589.8 11.168674 6.7314e−29 1.00000 N 0.208376 0.082117 NxGK CcCH 34.83.3 86.9 17.596286 3.5249e−26 1.00000 B 0.400460 0.038281 TxKT CcHH 39.54.3 154.6 17.143559 3.7891e−26 1.00000 B 0.255498 0.028007 NxAC EeCC27.0 2.0 50.4 18.153492 6.3631e−25 1.00000 B 0.535714 0.039237 TxAE ChHH127.2 56.2 609.9 9.932803 3.0165e−23 1.00000 N 0.208559 0.092199 FxNSChHH 27.7 2.3 55.4 16.958631 3.7819e−23 1.00000 B 0.500000 0.042157 GxTNCcHH 32.2 7.1 72.4 9.871338 1.9381e−22 1.00000 N 0.444751 0.098713 QxGKCcCH 29.0 3.4 42.7 14.374481 3.4874e−22 1.00000 B 0.679157 0.080540 GxSTChHH 55.4 16.7 309.3 9.733730 3.7002e−22 1.00000 N 0.179114 0.054010TxAQ ChHH 65.5 22.0 303.2 9.611531 1.0400e−21 1.00000 N 0.2160290.072705 DxEG HhHC 38.2 9.8 91.3 9.586215 2.3137e−21 1.00000 N 0.4184010.107564 SxEE ChHH 251.6 144.3 1525.5 9.392189 4.4475e−21 1.00000 N0.164930 0.094565 SxKT CcHH 30.5 3.1 137.0 15.606960 5.0423e−21 1.00000B 0.222628 0.022952 NxRG CeCC 26.1 5.5 50.1 9.307237 5.3638e−20 1.00000N 0.520958 0.109822 KxDK EeEE 103.4 45.3 400.6 9.155613 5.5926e−201.00000 N 0.258113 0.113187 KxTG HhHC 76.9 30.0 329.0 8.9787733.2532e−19 1.00000 N 0.233739 0.091216 SxTK HcEE 87.3 36.5 320.28.926379 4.8515e−19 1.00000 N 0.272642 0.114065 FxGH CcCH 12.2 0.2 23.125.026094 1.0525e−18 1.00000 B 0.528139 0.010002 GxTS ChHH 29.2 6.7121.4 8.949970 1.0560e−18 1.00000 N 0.240527 0.055132 CxAG CcCC 36.3 9.5225.9 8.891002 1.3288e−18 1.00000 N 0.160691 0.042014 GxGR CcCH 30.7 7.3148.4 8.862278 2.1091e−18 1.00000 N 0.206873 0.049330 TxVD EeEE 116.554.9 674.4 8.681155 3.6299e−18 1.00000 N 0.172746 0.081358 PxWN CeEC13.5 0.6 14.0 17.598010 4.8699e−18 1.00000 B 0.964286 0.040219 AxGL HcCC79.5 32.1 539.5 8.617327 7.5507e−18 1.00000 N 0.147359 0.059556 SxYQChHH 24.4 5.2 78.1 8.742181 8.3452e−18 1.00000 N 0.312420 0.066298 RxNGEeCC 51.7 17.5 171.1 8.620737 9.9272e−18 1.00000 N 0.302162 0.102376QxPN HcHH 26.8 6.3 56.5 8.705318 1.0034e−17 1.00000 N 0.474336 0.110806GxLA CcCE 25.1 2.7 98.2 13.717935 2.3659e−17 1.00000 B 0.255601 0.027844TxNR ChHH 29.0 4.4 76.1 12.133203 6.1385e−17 1.00000 B 0.381078 0.057443TxEE ChHH 243.4 147.4 1546.4 8.314461 6.6330e−17 1.00000 N 0.1573980.095312 NxAL ChHH 30.5 7.7 168.3 8.377216 1.2719e−16 1.00000 N 0.1812240.045980 TxTG CcCC 114.1 55.4 731.8 8.204551 2.0652e−16 1.00000 N0.155917 0.075694 SxKS CcHH 27.2 6.5 176.6 8.271558 3.4649e−16 1.00000 N0.154020 0.036814 WxGP CcHH 27.2 4.5 50.2 11.245730 5.9545e−16 1.00000 B0.541833 0.089269 GxSS ChHH 25.9 6.1 149.4 8.136343 1.0923e−15 1.00000 N0.173360 0.041144 SxAD ChHH 93.1 42.9 534.3 7.998864 1.1948e−15 1.00000N 0.174247 0.080239 PxNV ChHH 25.4 6.1 97.5 8.121634 1.2689e−15 1.00000N 0.260513 0.062064 QxTG HhHC 36.3 10.8 146.5 8.059476 1.3787e−151.00000 N 0.247782 0.073749 NxCN CcCC 27.4 6.9 110.2 8.055912 1.9302e−151.00000 N 0.248639 0.062659 GxGL CcCH 28.6 7.4 180.7 7.990101 3.0473e−151.00000 N 0.158273 0.040752 QxNT CeCC 22.2 3.4 31.0 10.894909 3.4768e−151.00000 B 0.716129 0.108225 GxGF EcCE 16.8 1.2 40.5 14.399043 3.7361e−151.00000 B 0.414815 0.029841 TxEQ ChHH 131.0 69.3 722.9 7.7994285.1196e−15 1.00000 N 0.181215 0.095827 ExLG HhHC 117.4 59.7 783.87.773841 6.4656e−15 1.00000 N 0.149783 0.076139 MxIF CcHH 24.6 3.6 56.811.457873 6.4773e−15 1.00000 B 0.433099 0.063193 LxHA CcEE 11.8 0.4 33.319.335145 7.4581e−15 1.00000 B 0.354354 0.010636 MxLC EeCC 9.0 0.2 15.122.286623 8.2126e−15 1.00000 B 0.596026 0.010533 SxLP HhCC 41.8 13.8235.1 7.791006 9.8874e−15 1.00000 N 0.177797 0.058524 SxKV CeEE 74.832.8 361.7 7.687742 1.5248e−14 1.00000 N 0.206801 0.090709 YxTM CcCE19.6 2.1 43.7 12.252047 2.0037e−14 1.00000 B 0.448513 0.048882 DxCQ EcCC15.9 1.0 105.6 14.568386 3.6015e−14 1.00000 B 0.150568 0.009939 LxDWEcCC 10.1 0.3 23.0 18.614550 6.7635e−14 1.00000 B 0.439130 0.012246 RxGLHhCC 42.9 15.0 220.2 7.477473 1.0395e−13 1.00000 N 0.194823 0.067983SxEQ ChHH 106.6 54.0 926.8 7.379054 1.3464e−13 1.00000 N 0.1150190.058249 VxKT CcHH 25.3 3.9 163.9 10.987962 1.5771e−13 1.00000 B0.154362 0.023729 YxSG HhCC 28.3 8.0 122.7 7.457246 1.7456e−13 1.00000 N0.230644 0.064853 NxGY EcCC 21.7 3.1 58.1 10.941103 2.7368e−13 1.00000 B0.373494 0.052720 GxFM CcCH 10.0 0.5 10.7 13.642568 3.2977e−13 1.00000 B0.934579 0.047496 SxMS CcEE 14.9 1.1 51.5 13.353266 3.9684e−13 1.00000 B0.289320 0.021211 YxGD EeCC 25.4 6.8 119.1 7.343589 4.4620e−13 1.00000 N0.213266 0.057113 NxLP HhCC 31.4 9.5 153.2 7.304107 4.7698e−13 1.00000 N0.204961 0.062314 NxED ChHH 68.8 30.8 317.4 7.204843 5.8007e−13 1.00000N 0.216761 0.097047 SxDE ChHH 97.5 49.7 519.2 7.121477 9.1460e−131.00000 N 0.187789 0.095803 YxGS EcCC 36.1 12.1 183.1 7.1356841.4043e−12 1.00000 N 0.197160 0.066120 RxHG HhHC 25.6 7.2 82.9 7.1660511.5713e−12 1.00000 N 0.308806 0.086994 AxGK CcCH 26.4 7.4 177.4 7.1176632.1019e−12 1.00000 N 0.148816 0.041830 SxSE ChHH 61.7 26.9 315.17.001886 2.5790e−12 1.00000 N 0.195811 0.085508 DxVT EeEE 24.9 6.8 171.07.088115 2.7435e−12 1.00000 N 0.145614 0.039734 PxKC CcCH 12.3 1.3 12.510.266594 3.6601e−12 1.00000 B 0.984000 0.102657 KxLG HhHC 102.4 53.8672.1 6.913764 3.8864e−12 1.00000 N 0.152358 0.080006 RxSE EeCC 29.1 8.9141.3 7.008188 4.1037e−12 1.00000 N 0.205945 0.062855 TxNI EeCC 15.3 1.725.9 10.648995 6.3319e−12 1.00000 B 0.590734 0.067123 AxGF HcCC 33.511.1 222.8 6.917099 6.7617e−12 1.00000 N 0.150359 0.049674 PxSQ ChHH31.3 10.2 111.0 6.920163 7.0916e−12 1.00000 N 0.281982 0.092073 ExLPHhCC 42.2 15.8 295.8 6.839588 9.7186e−12 1.00000 N 0.142664 0.053319KxHG HhCC 42.9 16.6 163.8 6.820623 1.1077e−11 1.00000 N 0.2619050.101187 GxGR CcHH 20.4 3.0 109.2 10.222967 1.2503e−11 1.00000 B0.186813 0.027325 VxHG CcEE 7.8 0.1 17.8 19.977321 1.5310e−11 1.00000 B0.438202 0.008312 DxAS ChHH 45.9 18.2 275.4 6.736084 1.8618e−11 1.00000N 0.166667 0.065934 ExFG HhHC 57.0 24.7 365.9 6.717061 1.8836e−111.00000 N 0.155780 0.067613 ExSG HhHC 34.0 11.8 154.5 6.7511392.0640e−11 1.00000 N 0.220065 0.076071 RxTG HhHC 45.1 17.9 213.76.711082 2.2341e−11 1.00000 N 0.211044 0.083822 ExTG HhHC 52.2 22.0309.4 6.677412 2.5699e−11 1.00000 N 0.168714 0.071133 NxAQ ChHH 32.711.2 137.8 6.713106 2.7429e−11 1.00000 N 0.237300 0.081146 SxQE ChHH54.8 23.8 271.3 6.647848 3.0642e−11 1.00000 N 0.201990 0.087780 CxSCCcCH 7.0 0.1 36.8 20.082842 3.1318e−11 1.00000 B 0.190217 0.003201 FxTNEcCC 19.5 3.0 66.8 9.782338 3.5580e−11 1.00000 B 0.291916 0.044669 TxNGEeCC 49.7 20.7 275.2 6.622482 3.8018e−11 1.00000 N 0.180596 0.075273PxDQ ChHH 43.8 17.5 180.6 6.602266 4.6907e−11 1.00000 N 0.2425250.097075 QxVI CcCC 24.5 7.2 107.7 6.666417 4.7835e−11 1.00000 N 0.2274840.066942 ExGG EeCC 45.4 18.2 306.7 6.559515 6.0218e−11 1.00000 N0.148027 0.059455

TABLE 10 In Expected P-Value P-Value Observed Null Sequence StructureEpitopes in Epi In PDB Z-Score Upper Lower Distribution RatioProbability GKxT CHhH 137.0 18.6 556.5 27.928770  1.6042e−170 1.00000 N0.246181 0.033414 GKxS CHhH 56.2 5.0 184.9 23.104150  3.8172e−1161.00000 N 0.303948 0.027261 TGxT CChH 69.6 9.6 241.3 19.7179261.9252e−85 1.00000 N 0.288438 0.039924 VGxS CChH 50.5 6.3 209.217.879802 3.1232e−70 1.00000 N 0.241396 0.030118 NKxD ECcC 74.1 12.7233.0 17.719652 1.9024e−69 1.00000 N 0.318026 0.054503 GSxK CCcH 46.56.2 194.2 16.436360 1.4881e−59 1.00000 N 0.239444 0.031966 GVxK CCcH55.3 9.0 278.3 15.716574 8.3454e−55 1.00000 N 0.198706 0.032256 CKxGCCcC 51.5 11.1 173.9 12.558736 1.2519e−35 1.00000 N 0.296147 0.063651GTxK CCcH 35.3 5.8 178.9 12.475785 7.0287e−35 1.00000 N 0.1973170.032332 GFxN CChH 31.2 5.6 56.9 11.416464 2.1905e−29 1.00000 N 0.5483300.098116 WCxP CChH 33.3 2.6 62.5 19.373109 4.2055e−29 1.00000 B 0.5328000.041887 FTxS CHhH 27.7 2.2 52.5 17.490092 6.0171e−24 1.00000 B 0.5276190.042219 NVxC EEcC 26.5 1.9 52.2 17.922628 8.5115e−24 1.00000 B 0.5076630.037341 VAxK ECcC 33.3 7.2 90.1 10.147731 1.2188e−23 1.00000 N 0.3695890.079833 SGxT CChH 34.7 7.7 211.7 9.940448 8.6460e−23 1.00000 N 0.1639110.036237 AGxT CChH 36.4 4.4 143.7 15.434531 9.7685e−23 1.00000 B0.253305 0.030811 GGxM CCcH 30.4 3.0 94.6 16.207156 2.5281e−22 1.00000 B0.321353 0.031282 SGxS CChH 27.3 5.3 185.2 9.755693 7.5361e−22 1.00000 N0.147408 0.028376 ERxG HHcC 76.1 28.0 265.7 9.603856 1.0100e−21 1.00000N 0.286413 0.105454 DSxE CChH 66.0 22.6 239.7 9.582583 1.3711e−211.00000 N 0.275344 0.094387 RExG HHhC 92.3 37.7 353.8 9.4183905.1848e−21 1.00000 N 0.260882 0.106451 DSxT EEeE 32.3 7.5 89.0 9.4704658.5068e−21 1.00000 N 0.362921 0.084184 QFxT CEcC 21.3 1.6 29.7 16.0616169.1250e−21 1.00000 B 0.717172 0.053568 GAxK CCcH 35.5 5.0 135.713.978985 2.4411e−20 1.00000 B 0.261606 0.036517 VGxT CChH 29.1 6.4179.3 9.116224 2.4335e−19 1.00000 N 0.162298 0.035804 NQxP HHcH 28.5 6.658.0 9.017809 6.1701e−19 1.00000 N 0.491379 0.114435 TKxD EEeE 103.546.7 416.7 8.823218 1.1095e−18 1.00000 N 0.248380 0.112045 QAxG HHcC58.1 20.4 220.9 8.766703 2.5643e−18 1.00000 N 0.263015 0.092292 KVxKEEeE 129.0 63.4 665.5 8.662445 4.1119e−18 1.00000 N 0.193839 0.095260IDxS ECcE 41.4 12.0 221.9 8.712627 5.4346e−18 1.00000 N 0.1865710.054175 STxV CEeE 79.7 33.6 368.4 8.334380 8.3322e−17 1.00000 N0.216341 0.091281 FYxM CCcE 1.0 0.1 1.0 3.846944 1.0400e−16 1.00000 B1.000000 0.063295 NIxM HCcC 1.0 0.0 1.0 4.415241 1.0561e−16 1.00000 B1.000000 0.048794 PTxN CEeC 15.5 1.1 17.1 14.132918 1.0977e−16 1.00000 B0.906433 0.064841 NKxG HHhC 32.2 8.7 87.3 8.377682 1.2095e−16 1.00000 N0.368843 0.099933 NKxD EChH 24.2 5.3 121.7 8.342068 2.3144e−16 1.00000 N0.198850 0.043910 YAxG HHcC 30.2 7.8 110.3 8.294939 2.5405e−16 1.00000 N0.273799 0.070980 YSxM CCcE 23.7 2.8 61.6 12.840494 3.5944e−16 1.00000 B0.384740 0.045127 ACxN CCcC 23.9 5.4 105.8 8.125941 1.3307e−15 1.00000 N0.225898 0.051421 RRxG HHhC 58.0 22.3 215.4 7.997367 1.5668e−15 1.00000N 0.269266 0.103372 FPxH CCcH 12.5 0.5 22.2 17.814824 2.2978e−15 1.00000B 0.563063 0.020995 VSxG EEeC 28.5 7.3 361.1 7.916574 5.3875e−15 1.00000N 0.078926 0.020248 RAxG HHcC 86.6 40.4 412.0 7.653312 1.8592e−141.00000 N 0.210194 0.098060 KDxG HHhC 61.6 25.2 236.0 7.6605312.0910e−14 1.00000 N 0.261017 0.106924 SSxK HCeE 57.9 23.2 198.27.653307 2.2980e−14 1.00000 N 0.292129 0.117242 RRxG HHcC 56.3 22.3211.9 7.619259 3.0185e−14 1.00000 N 0.265691 0.105141 KKxG HHhC 87.741.5 381.6 7.588969 3.0299e−14 1.00000 N 0.229822 0.108834 GSxW EChH11.0 0.3 38.1 18.116766 3.7547e−14 1.00000 B 0.288714 0.009156 GLxP CCcH48.9 17.8 319.3 7.570949 4.6990e−14 1.00000 N 0.153148 0.055852 KGxGCChH 21.6 5.0 71.7 7.659772 5.4871e−14 1.00000 N 0.301255 0.070178 KQxTCEeE 26.1 4.9 50.9 10.135942 5.6397e−14 1.00000 B 0.512770 0.095404 ARxPHHcC 39.6 13.4 140.5 7.511607 8.6527e−14 1.00000 N 0.281851 0.095553ETxS ECcC 29.2 8.4 99.1 7.526295 1.0238e−13 1.00000 N 0.294652 0.084439DKxG HHhC 59.5 24.9 228.9 7.356353 2.0816e−13 1.00000 N 0.2599390.108634 KPxY CCcC 42.7 15.2 188.2 7.350314 2.6651e−13 1.00000 N0.226886 0.080837 QTxK CCcH 17.8 2.2 26.3 10.850825 3.1717e−13 1.00000 B0.676806 0.085419 RSxG HHcC 54.3 22.0 224.4 7.250022 4.7424e−13 1.00000N 0.241979 0.098051 KMxF CCcC 23.1 6.0 83.2 7.217699 1.2237e−12 1.00000N 0.277644 0.072479 RKxG HHhC 59.6 25.6 254.0 7.098040 1.3380e−121.00000 N 0.234646 0.100650 EExG HHhC 98.4 50.6 520.0 7.0659141.3554e−12 1.00000 N 0.189231 0.097369 AAxG HHhC 75.4 35.0 497.17.073599 1.4144e−12 1.00000 N 0.151680 0.070477 LSxE CChH 112.6 60.1832.4 7.032831 1.6319e−12 1.00000 N 0.135272 0.072187 KAxG HHcC 86.743.1 434.8 7.007685 2.1431e−12 1.00000 N 0.199402 0.099021 MNxF CChH25.2 4.9 62.4 9.506941 2.2013e−12 1.00000 B 0.403846 0.079074 LTxW ECcC10.1 0.4 19.7 15.073737 2.2502e−12 1.00000 B 0.512690 0.021385 NPxE CCcH23.8 6.4 92.8 7.124827 2.2574e−12 1.00000 N 0.256466 0.069004 WLxV EEcC11.0 0.8 12.3 11.619322 2.4161e−12 1.00000 B 0.894309 0.066848 GVxF CEeE20.8 5.1 180.9 7.100474 3.1004e−12 1.00000 N 0.114981 0.027956 SAxG HHhC37.8 13.3 158.5 7.005915 3.3764e−12 1.00000 N 0.238486 0.084068 CGxCCEcH 10.3 0.4 33.8 15.665276 3.9680e−12 1.00000 B 0.304734 0.011950 GSxWCChH 13.8 1.0 55.6 12.942109 4.0102e−12 1.00000 B 0.248201 0.017924 KNxAEEeC 20.4 5.2 50.6 7.054783 4.4588e−12 1.00000 N 0.403162 0.102437 EAxGHHcC 82.7 40.7 436.1 6.903283 4.5200e−12 1.00000 N 0.189635 0.093429GKxA CHhH 32.0 10.2 237.0 6.946622 5.7267e−12 1.00000 N 0.1350210.043241 QKxG HHhC 50.3 20.7 190.7 6.898030 5.9432e−12 1.00000 N0.263765 0.108445 FMxQ CEeE 13.1 0.9 62.3 12.683560 7.8246e−12 1.00000 B0.210273 0.014993 LAxG HHcC 73.6 34.7 547.8 6.815209 8.6277e−12 1.00000N 0.134356 0.063400 FNxN ECcC 20.7 5.2 107.5 6.950636 8.7080e−12 1.00000N 0.192558 0.048520 TQxG HHcC 23.6 6.7 73.0 6.857650 1.4179e−11 1.00000N 0.323288 0.091676 TWxI EEcC 12.3 1.2 15.1 10.555052 1.8885e−11 1.00000B 0.814570 0.079552 WGxG ECcC 39.1 14.1 669.1 6.742288 1.9532e−111.00000 N 0.058437 0.021034 DRxG HHhC 37.3 13.7 145.5 6.7100082.5502e−11 1.00000 N 0.256357 0.094011 GDxT CCcE 34.9 12.3 154.96.715037 2.5763e−11 1.00000 N 0.225307 0.079419 PFxA CCcH 20.8 3.5 66.69.476040 3.8082e−11 1.00000 B 0.312312 0.052751 DHxK CCcH 14.5 1.4 46.311.115290 3.8920e−11 1.00000 B 0.313175 0.030826 ISxE CChH 56.6 24.8386.1 6.605482 3.9718e−11 1.00000 N 0.146594 0.064198 RMxT HHcC 13.8 1.424.9 10.680289 4.2758e−11 1.00000 B 0.554217 0.057195 ANxP HHcC 30.610.3 110.0 6.640679 4.6760e−11 1.00000 N 0.278182 0.093685 LSxG HHcC39.7 15.0 242.9 6.598851 5.0502e−11 1.00000 N 0.163442 0.061625 GLxRCHhH 21.8 5.9 145.6 6.672827 5.1373e−11 1.00000 N 0.149725 0.040593 YWxDCCeE 6.6 0.1 6.5 18.333825 6.7702e−11 1.00000 B 1.015385 0.018971 DAxGHHhC 38.6 14.7 177.7 6.514124 8.9759e−11 1.00000 N 0.217220 0.082658QGxG CChH 17.2 2.5 46.0 9.594800 9.0059e−11 1.00000 B 0.373913 0.054045EGxT ECcE 26.5 8.5 78.0 6.552315 9.4222e−11 1.00000 N 0.339744 0.108760SGxW CCcE 20.7 5.6 91.2 6.551699 1.1925e−10 1.00000 N 0.226974 0.061790KExG HHhC 110.3 62.5 581.6 6.398256 1.2154e−10 1.00000 N 0.1896490.107478 QExG HHhC 44.7 18.4 194.8 6.446972 1.2707e−10 1.00000 N0.229466 0.094406 KSxW CChH 17.5 2.5 59.4 9.591293 1.6500e−10 1.00000 B0.294613 0.042780 CGxC CCcH 9.9 0.5 42.7 13.508852 1.7531e−10 1.00000 B0.231850 0.011494

TABLE 11 In Expected P-Value P-Value Observed Null Sequence StructureEpitopes in Epi In PDB Z-Score Upper Lower Distribution RatioProbability GKTT CHHH 76.5 5.5 253.6 30.574180  9.6042e−203 1.00000 N0.301656 0.021730 GKST CHHH 46.3 5.3 197.6 18.047241 2.1757e−71 1.00000N 0.234312 0.026836 VGKS CCHH 47.9 1.7 155.8 35.415804 7.1871e−541.00000 B 0.307445 0.011035 AGKT CCHH 35.5 0.7 86.1 40.746053 2.0004e−491.00000 B 0.412311 0.008528 GVGK CCCH 47.2 2.5 185.6 28.1706509.8957e−45 1.00000 B 0.254310 0.013725 GSGK CCCH 41.1 2.5 156.824.822233 1.5821e−37 1.00000 B 0.262117 0.015699 TGKT CCHH 39.3 2.7129.9 22.607690 4.6581e−34 1.00000 B 0.302540 0.020625 VACK ECCC 33.22.4 45.0 20.373654 1.4230e−32 1.00000 B 0.737778 0.053619 CSAG CCCC 18.60.2 56.3 45.155914 2.7647e−32 1.00000 B 0.330373 0.002969 KVDK EEEE 99.735.9 374.1 11.193395 5.8880e−29 1.00000 N 0.266506 0.096012 TKVD EEEE98.5 36.0 385.6 10.933259 1.0444e−27 1.00000 N 0.255446 0.093416 GAGKCCCH 28.8 1.8 99.9 20.625737 2.2129e−26 1.00000 B 0.288288 0.017523 CKNGCCCC 32.8 3.1 60.3 17.224893 5.4973e−26 1.00000 B 0.543947 0.051900 STKVCEEE 69.5 22.3 234.9 10.494679 1.4747e−25 1.00000 N 0.295871 0.095048GSCW CCHH 12.8 0.1 33.8 46.433544 1.4522e−24 1.00000 B 0.378698 0.002227NVAC EECC 26.5 1.9 49.4 18.344959 1.9069e−24 1.00000 B 0.536437 0.037918GKTS CHHH 25.4 1.6 64.9 19.094604 8.3481e−24 1.00000 B 0.391371 0.024554SGKT CCHH 28.0 2.2 126.7 17.503774 1.0663e−22 1.00000 B 0.2209940.017439 GTGK CCCH 28.6 2.3 128.1 17.567876 1.1598e−22 1.00000 B0.223263 0.017834 FTNS CHHH 25.7 2.1 47.2 16.829282 2.2403e−22 1.00000 B0.544492 0.043704 GSCW ECHH 11.0 0.1 27.3 39.303420 1.3941e−21 1.00000 B0.402930 0.002837 SGKS CCHH 21.9 1.2 111.0 19.363958 3.2639e−21 1.00000B 0.197297 0.010445 VGKT CCHH 25.3 1.9 136.0 17.189134 7.3292e−211.00000 B 0.186029 0.013839 DKEG HHHC 26.2 5.5 57.6 9.268980 7.4842e−201.00000 N 0.454861 0.095656 FPGH CCCH 11.5 0.2 16.2 28.669589 1.9821e−191.00000 B 0.709877 0.009756 WCGP CCHH 23.2 2.1 48.1 14.990162 3.7261e−191.00000 B 0.482328 0.043149 GFTN CCHH 28.4 4.0 44.3 12.702991 6.0926e−191.00000 B 0.641084 0.091314 LTDW ECCC 10.1 0.1 11.0 26.776988 1.1021e−181.00000 B 0.918182 0.012740 PGPP CCCC 27.7 3.6 50.4 13.137686 1.2393e−181.00000 B 0.549603 0.071817 QFNT CECC 19.8 1.6 28.2 15.038708 1.4634e−181.00000 B 0.702128 0.055230 TQTG CCCC 23.0 2.4 39.9 13.827921 1.8451e−181.00000 B 0.576441 0.059320 LNHA CCEE 11.1 0.2 20.0 25.694482 5.0337e−181.00000 B 0.555000 0.009110 GKSS CHHH 19.2 1.2 65.2 16.561873 5.3468e−181.00000 B 0.294479 0.018451 QHFK EEEE 15.5 1.0 16.0 14.980105 6.5038e−181.00000 B 0.968750 0.062464 SSTK HCEE 54.6 18.9 198.1 8.6406827.9973e−18 1.00000 N 0.275618 0.095330 RWNR CCCH 2.0 0.2 2.0 4.8932703.1595e−17 1.00000 B 1.000000 0.077089 NVGK CCCH 13.5 0.4 31.0 20.3351664.2581e−17 1.00000 B 0.435484 0.013530 ACKN CCCC 22.1 2.3 44.0 13.3519704.5720e−17 1.00000 B 0.502273 0.052665 NAGK CCCH 9.8 0.1 18.7 30.3504796.7477e−17 1.00000 B 0.524064 0.005489 HTFI ECCC 1.0 0.1 1.0 3.3758351.0207e−16 1.00000 B 1.000000 0.080669 EAHV CCCE 1.0 0.1 1.0 3.9215141.0424e−16 1.00000 B 1.000000 0.061056 FADK EEEC 1.5 0.1 1.0 3.9997961.0449e−16 1.00000 B 1.500000 0.058829 FHIS HCCC 1.8 0.1 1.0 4.0202281.0455e−16 1.00000 B 1.800000 0.058267 ADKL EECC 1.7 0.1 1.0 4.0620221.0468e−16 1.00000 B 1.700000 0.057143 AGKS CCHH 14.6 0.6 40.6 18.6841591.0527e−16 1.00000 B 0.359606 0.014083 TFGK ECCH 1.0 0.0 1.0 4.7636631.0634e−16 1.00000 B 1.000000 0.042207 ANHI HHCC 1.0 0.0 1.0 4.9670511.0670e−16 1.00000 B 1.000000 0.038954 YIKI EECC 1.5 0.0 1.0 5.7224461.0773e−16 1.00000 B 1.500000 0.029633 AGMD CCEC 1.3 0.0 1.0 6.8507901.0871e−16 1.00000 B 1.300000 0.020862 LFLE CHHH 1.0 0.0 1.0 7.2224291.0893e−16 1.00000 B 1.000000 0.018810 VATS ECHH 1.5 0.0 1.0 19.6874471.1074e−16 1.00000 B 1.500000 0.002573 GLGF ECCE 8.5 0.1 11.4 32.4511802.0417e−16 1.00000 B 0.745614 0.005958 QEVI CCCC 17.0 1.4 24.7 13.6958612.5094e−16 1.00000 B 0.688259 0.055787 MELC EECC 9.0 0.1 12.1 25.4656082.7631e−16 1.00000 B 0.743802 0.010146 MDSS ECCC 14.9 0.7 43.2 17.3574204.1795e−16 1.00000 B 0.344907 0.015781 QTGK CCCH 16.3 1.5 18.2 12.7056454.9345e−16 1.00000 B 0.895604 0.081365 PSVY CEEE 17.5 1.1 268.715.823536 1.2792e−15 1.00000 B 0.065128 0.004023 TPNR CHHH 22.0 2.6 54.212.385370 1.5783e−15 1.00000 B 0.405904 0.047623 KPLY CCCC 17.3 1.9 20.111.920519 1.7658e−15 1.00000 B 0.860697 0.092045 GNLA CCCE 10.0 0.3 11.018.159308 1.9656e−15 1.00000 B 0.909091 0.026686 AAGK CCCH 13.3 0.6 36.116.855814 5.6027e−15 1.00000 B 0.368421 0.016035 YSTM CCCE 19.6 2.1 42.712.437257 1.1609e−14 1.00000 B 0.459016 0.048830 MNIF CCHH 20.6 2.5 41.111.694370 2.3532e−14 1.00000 B 0.501217 0.061842 TGNT CCHH 13.5 0.9 18.914.035756 2.9887e−14 1.00000 B 0.714286 0.045000 NICR CCCH 5.0 0.0 10.862.091204 3.1714e−14 1.00000 B 0.462963 0.000599 QDKE HHHH 23.7 5.9 64.07.716774 3.1832e−14 1.00000 N 0.370312 0.091796 FNTN ECCC 18.2 1.9 37.612.129079 3.7927e−14 1.00000 B 0.484043 0.050580 SGRT CCCC 23.0 5.5 88.87.691022 3.9756e−14 1.00000 N 0.259009 0.062075 YRDV CCCC 15.5 1.2 27.613.113855 5.0190e−14 1.00000 B 0.561594 0.044865 VNHG CCEE 7.8 0.1 9.026.302593 5.5620e−14 1.00000 B 0.866667 0.009648 VDKK EEEE 78.6 36.1374.6 7.428060 1.0634e−13 1.00000 N 0.209824 0.096500 GKSA CHHH 15.8 1.256.8 13.676079 1.1247e−13 1.00000 B 0.278169 0.020574 GLTD EECC 10.6 0.511.4 14.766307 1.9385e−13 1.00000 B 0.929825 0.042968 FTVA CCHH 13.1 0.919.6 12.935319 2.1141e−13 1.00000 B 0.668367 0.047415 GGFM CCCH 10.0 0.510.7 13.957613 2.1432e−13 1.00000 B 0.934579 0.045486 PPGP CCCC 25.6 4.382.9 10.497601 2.2505e−13 1.00000 B 0.308806 0.052246 PTWN CEEC 13.5 0.510.5 13.872045 2.4774e−13 1.00000 B 1.285714 0.051741 STMS CCEE 14.9 1.142.8 13.377328 2.6426e−13 1.00000 B 0.348131 0.025541 GVCS CHHH 7.5 0.113.0 26.334228 2.7609e−13 1.00000 B 0.576923 0.006145 YASG HHCC 17.3 1.936.0 11.586737 3.4799e−13 1.00000 B 0.480556 0.051958 GGLM CCCH 12.2 0.719.9 13.592519 4.8030e−13 1.00000 B 0.613065 0.037107 DACQ ECCC 7.1 0.126.6 26.117565 7.6453e−13 1.00000 B 0.266917 0.002729 GLGR CHHH 11.0 0.616.8 13.543928 1.2177e−12 1.00000 B 0.654762 0.036346 VSWG EEEC 13.9 0.9142.4 13.792449 1.5390e−12 1.00000 B 0.097612 0.006283 DSVT EEEE 20.63.2 45.4 10.115672 2.6490e−12 1.00000 B 0.453744 0.070196 GIMS CHHH 5.00.0 5.0 31.463022 3.2056e−12 1.00000 B 1.000000 0.005026 SGVG CCCC 20.65.0 135.3 7.083857 3.5288e−12 1.00000 N 0.152254 0.037119 WNIG ECCC 12.30.5 9.3 12.738906 6.1148e−12 1.00000 B 1.322581 0.054202 DSCQ ECCC 7.80.1 72.0 22.511242 8.3027e−12 1.00000 B 0.108333 0.001621 QTPN HCHH 22.14.1 46.3 9.249495 8.5114e−12 1.00000 B 0.477322 0.089425 KSRW CCHH 15.61.6 45.6 11.351320 8.7811e−12 1.00000 B 0.342105 0.034653 STVE EEEE 17.02.4 30.0 9.755365 1.1687e−11 1.00000 B 0.566667 0.080927 ACNG CCCC 7.00.2 9.0 17.192673 2.0549e−11 1.00000 B 0.777778 0.017901 GACW ECHH 5.70.0 4.0 40.933013 3.2174e−11 1.00000 B 1.425000 0.002382 GVGR CCHH 7.30.1 23.6 19.823519 3.2681e−11 1.00000 B 0.309322 0.005572 AGIG CCCH 5.90.0 26.5 30.927404 3.4380e−11 1.00000 B 0.222642 0.001358 HGKT CCHH 8.00.2 36.2 16.510870 5.6930e−11 1.00000 B 0.220994 0.006166 TLIS EEEE 13.71.3 44.6 11.229338 7.1321e−11 1.00000 B 0.307175 0.028307 NTKV CEEE 38.014.4 156.3 6.545601 7.4133e−11 1.00000 N 0.243122 0.091884

TABLE 12 In Expected P-Value P-Value Observed Null Sequence StructureEpitopes in Epi In PDB Z-Score Upper Lower Distribution RatioProbability ExxxR HhhhH 3545.7 1634.5 12751.1 50.628214 0.0000e+001.00000 N 0.278070 0.128187 RxxxE HhhhH 2928.1 1427.8 11214.8 42.5030450.0000e+00 1.00000 N 0.261092 0.127313 QxxxD HhhhH 1521.3 666.8 5548.235.277704 1.3372e−272 1.00000 N 0.274197 0.120187 RxxxR HhhhH 1627.7735.0 5837.9 35.218117 1.0581e−271 1.00000 N 0.278816 0.125905 ExxxEHhhhH 2968.6 1676.2 12774.8 33.866288 1.6289e−251 1.00000 N 0.2323790.131213 DxxxR HhhhH 1593.6 739.8 6057.4 33.503679 4.1121e−246 1.00000 N0.263083 0.122130 ExxxQ HhhhH 1903.9 965.9 7773.1 32.250622 3.0026e−2281.00000 N 0.244934 0.124264 AxxxR HhhhH 1716.6 888.8 9975.9 29.0935713.6109e−186 1.00000 N 0.172075 0.089093 QxxxR HhhhH 1090.8 488.7 4100.829.020942 3.6056e−185 1.00000 N 0.265997 0.119170 AxxxA HhhhH 2239.11243.1 25522.9 28.964033 1.4239e−184 1.00000 N 0.087729 0.048705 QxxxQHhhhH 1076.2 488.7 4171.0 28.285687 5.1236e−176 1.00000 N 0.2580200.117162 QxxxE HhhhH 1661.6 884.6 7199.7 27.894386 2.5759e−171 1.00000 N0.230787 0.122866 ExxxA HhhhH 2448.2 1446.9 14973.0 27.6967985.5984e−169 1.00000 N 0.163508 0.096632 AxxxQ HhhhH 1200.9 575.4 6408.227.329373 1.7264e−164 1.00000 N 0.187401 0.089798 RxxxQ HhhhH 1065.6500.0 4150.3 26.972525 2.9554e−160 1.00000 N 0.256753 0.120469 ExxxKHhhhH 3252.3 2124.9 15568.8 26.317913 8.1352e−153 1.00000 N 0.2088990.136488 ExxxL HhhhH 1724.7 952.4 13302.4 25.973127 7.7159e−149 1.00000N 0.129653 0.071595 QxxxN HhhhH 782.6 336.4 3046.6 25.795862 1.0406e−1461.00000 N 0.256877 0.110409 KxxxE HhhhH 2766.8 1765.1 13152.5 25.6249115.5898e−145 1.00000 N 0.210363 0.134200 RxxxL HhhhH 1346.1 698.5 9345.225.474971 3.0835e−143 1.00000 N 0.144042 0.074742 LxxxR HhhhH 1256.2640.3 9084.4 25.244635 1.0887e−140 1.00000 N 0.138281 0.070486 LxxxEHhhhH 1373.3 739.2 9254.6 24.314227 1.1055e−130 1.00000 N 0.1483910.079873 NxxxR HhhhH 648.3 270.4 2518.1 24.322629 1.2367e−130 1.00000 N0.257456 0.107389 RxxxD HhhhH 1124.8 579.6 4662.5 24.197519 2.0224e−1291.00000 N 0.241244 0.124320 ExxxN HhhhH 1238.3 662.5 5424.4 23.8746484.6110e−126 1.00000 N 0.228283 0.122138 ExxxS HhhhH 1260.4 676.4 5947.223.853305 7.6202e−126 1.00000 N 0.211932 0.113731 YxxxN HhhhH 359.7114.6 1469.5 23.835304 2.2944e−125 1.00000 N 0.244777 0.078017 AxxxEHhhhH 1813.4 1077.4 10751.7 23.638803 1.1253e−123 1.00000 N 0.1686620.100207 QxxxA HhhhH 1147.9 606.8 7180.5 22.960147 9.5018e−117 1.00000 N0.159864 0.084501 QxxxL HhhhH 851.0 410.1 7080.9 22.428266 1.8468e−1111.00000 N 0.120182 0.057922 NxxxQ HhhhH 622.8 276.1 2608.8 22.0702136.1727e−108 1.00000 N 0.238730 0.105815 KxxxD HhhhH 1559.9 937.5 7193.221.796348 1.8415e−105 1.00000 N 0.216858 0.130335 LxxxQ HhhhH 838.5412.3 6031.4 21.746653 6.4761e−105 1.00000 N 0.139022 0.068358 YxxxRHhhhH 507.5 207.9 2808.6 21.590025 2.4287e−103 1.00000 N 0.1806950.074032 PxxxR HhhhH 719.8 345.7 3048.4 21.371192 2.2826e−101 1.00000 N0.236124 0.113393 RxxxA HhhhH 1371.7 800.6 8918.1 21.157309 1.7498e−991.00000 N 0.153811 0.089769 YxxxK HhhhH 681.0 320.1 3778.3 21.0882129.4565e−99 1.00000 N 0.180240 0.084710 TxxxQ HhhhH 624.6 288.5 2880.620.861512 1.1458e−96 1.00000 N 0.216830 0.100147 DxxxE HhhhH 1501.2918.8 7072.8 20.599825 1.9838e−94 1.00000 N 0.212250 0.129901 SxxxRHhhhH 800.7 407.6 4098.8 20.521420 1.1851e−93 1.00000 N 0.1953500.099432 YxxxL HhhhH 540.6 236.8 6880.9 20.088526 9.0430e−90 1.00000 N0.078565 0.034417 RxxxN HhhhH 653.6 316.9 2892.5 20.040727 2.2101e−891.00000 N 0.225964 0.109571 KxxxR HhhhH 1011.6 569.9 4523.9 19.7919652.7224e−87 1.00000 N 0.223612 0.125972 DxxxQ HhhhH 930.8 512.8 4144.619.719888 1.1598e−86 1.00000 N 0.224581 0.123724 SxxxQ HhhhH 680.2 338.03360.0 19.626339 8.0947e−86 1.00000 N 0.202440 0.100596 VxxxE HhhhH776.9 402.6 5432.9 19.383764 8.7489e−84 1.00000 N 0.142999 0.074111SxxxE HhhhH 986.8 556.7 5025.9 19.331093 2.2728e−83 1.00000 N 0.1963430.110765 HxxxE HhhhH 519.1 238.2 2247.4 19.253484 1.2780e−82 1.00000 N0.230978 0.105970 AxxxD HhhhH 831.5 447.2 4633.8 19.121192 1.3547e−811.00000 N 0.179442 0.096500 AxxxS HhhhH 815.9 432.0 6889.2 19.0762533.1981e−81 1.00000 N 0.118432 0.062711 DxxxA HhhhH 1305.7 800.2 8841.718.737176 1.7447e−78 1.00000 N 0.147675 0.090505 LxxxE CchhH 488.7 220.53253.3 18.701598 4.6170e−78 1.00000 N 0.150217 0.067791 ExxxD HhhhH1027.9 600.3 4905.2 18.630742 1.3593e−77 1.00000 N 0.209553 0.122376SxxxA HhhhH 836.8 452.6 7696.8 18.615784 1.8805e−77 1.00000 N 0.1087210.058802 TxxxR HhhhH 665.8 341.1 3439.7 18.522474 1.1550e−76 1.00000 N0.193563 0.099169 IxxxE HhhhH 652.2 328.6 4866.2 18.486861 2.2361e−761.00000 N 0.134027 0.067526 SxxxH HhhhH 315.2 120.9 1433.7 18.4669324.5899e−76 1.00000 N 0.219851 0.084326 QxxxS HhhhH 623.3 314.0 3007.918.442239 5.2220e−76 1.00000 N 0.207221 0.104399 LxxxQ CchhH 328.0 127.51903.8 18.382341 2.1159e−75 1.00000 N 0.172287 0.066973 PxxxA HhhhH816.8 444.6 6116.7 18.331464 3.6493e−75 1.00000 N 0.133536 0.072684FxxxQ HhhhH 322.3 125.4 2057.5 18.151574 1.4421e−73 1.00000 N 0.1566460.060927 ExxxY HhhhH 629.3 321.2 3734.6 17.978943 2.4098e−72 1.00000 N0.168505 0.086016 YxxxQ HhhhH 376.9 159.4 2150.4 17.908928 1.0512e−711.00000 N 0.175270 0.074107 KxxxQ HhhhH 1012.7 602.6 4794.5 17.8668191.5795e−71 1.00000 N 0.211221 0.125685 VxxxR HhhhH 729.3 391.2 5584.017.726047 2.1028e−70 1.00000 N 0.130605 0.070058 IxxxN HhhhH 403.8 176.62697.7 17.686932 5.2702e−70 1.00000 N 0.149683 0.065459 NxxxE HhhhH854.2 488.3 4085.1 17.649644 7.8447e−70 1.00000 N 0.209101 0.119520ExxxI HhhhH 758.2 412.4 6102.5 17.633481 1.0697e−69 1.00000 N 0.1242440.067581 IxxxR HhhhH 603.5 306.0 4707.3 17.585071 2.6989e−69 1.00000 N0.128205 0.065013 CxxxH HhhhH 107.1 23.6 476.2 17.656516 2.9300e−691.00000 N 0.224906 0.049463 MxxxE CchhH 292.0 113.4 1275.4 17.5639165.5301e−69 1.00000 N 0.228948 0.088946 NxxxS HhhhH 514.3 251.1 2512.217.506813 1.1392e−68 1.00000 N 0.204721 0.099956 QxxxT HhhhH 555.2 279.92775.6 17.354733 1.5715e−67 1.00000 N 0.200029 0.100838 HxxxQ HhhhH327.4 136.5 1404.3 17.198608 2.9556e−66 1.00000 N 0.233141 0.097192VxxxN HhhhH 437.6 204.7 2937.8 16.882201 5.6161e−64 1.00000 N 0.1489550.069662 DxxxS HhhhH 723.1 404.9 3662.5 16.770933 3.1011e−63 1.00000 N0.197433 0.110539 DxxxD HhhhH 761.9 435.3 3587.0 16.698203 1.0362e−621.00000 N 0.212406 0.121362 SxxxS HhhhH 612.2 324.9 3868.8 16.6530772.3318e−62 1.00000 N 0.158240 0.083981 PxxxE HhhhH 874.8 522.0 4147.716.516679 2.0506e−61 1.00000 N 0.210912 0.125850 FxxxR HhhhH 380.5 171.42686.2 16.507278 3.1248e−61 1.00000 N 0.141650 0.063807 TxxxE HhhhH774.7 446.4 4237.2 16.426992 9.2564e−61 1.00000 N 0.182833 0.105356WxxxQ HhhhH 201.9 69.9 1001.1 16.362918 4.8607e−60 1.00000 N 0.2016780.069854 LxxxH HhhhH 363.9 162.7 3238.0 16.184271 6.2530e−59 1.00000 N0.112384 0.050250 IxxxQ HhhhH 400.2 186.3 3042.8 16.174438 7.0518e−591.00000 N 0.131524 0.061226 DxxxK HhhhH 1418.7 960.1 7235.1 15.8909604.8245e−57 1.00000 N 0.196086 0.132705 ExxxT HhhhH 863.4 520.4 5003.915.884514 5.8664e−57 1.00000 N 0.172545 0.103999 RxxxK HhhhH 1047.0667.3 5094.2 15.769294 3.5148e−56 1.00000 N 0.205528 0.130986 NxxxNHhhhH 411.8 201.8 1933.5 15.625829 4.3487e−55 1.00000 N 0.2129820.104345 HxxxR HhhhH 321.8 143.5 1583.7 15.607413 6.4283e−55 1.00000 N0.203195 0.090614 NxxxL HhhhH 450.7 223.9 4154.2 15.578085 8.7727e−551.00000 N 0.108493 0.053909 SxxxN HhhhH 487.3 253.1 2480.3 15.5347561.6921e−54 1.00000 N 0.196468 0.102045 DxxxN HhhhH 594.3 330.2 2767.715.489774 3.2073e−54 1.00000 N 0.214727 0.119292 ExxxH HhhhH 551.1 300.02737.5 15.360468 2.4145e−53 1.00000 N 0.201315 0.109602 YxxxE HhhhH396.8 192.7 2422.9 15.323125 4.7702e−53 1.00000 N 0.163771 0.079539LxxxN HhhhH 499.1 260.5 3907.2 15.305012 5.7912e−53 1.00000 N 0.1277390.066663 PxxxQ HhhhH 489.4 259.6 2215.5 15.182747 3.8046e−52 1.00000 N0.220898 0.117159 QxxxW HhhhH 165.8 55.6 973.5 15.206793 4.5631e−521.00000 N 0.170313 0.057164 ExxxR HhhhC 358.1 171.9 1395.4 15.1613625.9193e−52 1.00000 N 0.256629 0.123222 LxxxL HhhhH 997.1 625.8 27017.215.017249 3.8391e−51 1.00000 N 0.036906 0.023163

TABLE 13 In Expected P-Value P-Value Observed Null Sequence StructureEpitopes in Epi In PDB Z-Score Upper Lower Distribution RatioProbability NxxDL EccCC 52.0 5.7 142.7 19.794530 1.1279e−85 1.00000 N0.364401 0.039936 TxxGK CccCH 57.5 7.2 179.0 19.161164 1.4880e−801.00000 N 0.321229 0.040133 SxxYH HhhHH 55.1 7.3 104.0 18.2761802.0986e−73 1.00000 N 0.529808 0.070636 GxxKS CccHH 81.1 15.9 322.616.741561 2.8010e−62 1.00000 N 0.251395 0.049402 CxxCH HhhCC 51.8 7.9109.2 16.170548 7.9700e−58 1.00000 N 0.474359 0.072665 ExxRR HhhHH 299.8133.8 1539.6 15.024308 5.0311e−51 1.00000 N 0.194726 0.086878 CxxCHHhhHH 52.6 9.3 112.0 14.780082 1.2263e−48 1.00000 N 0.469643 0.083434SxxGK CccCH 44.6 6.8 222.2 14.731787 3.5333e−48 1.00000 N 0.2007200.030575 GxxKT CccHH 72.0 15.7 369.5 14.495654 4.1781e−47 1.00000 N0.194858 0.042587 AxxAA HhhHH 232.6 96.4 3380.2 14.070952 5.9399e−451.00000 N 0.068812 0.028524 CxxCH ChhHH 41.5 2.9 62.5 23.3027959.4544e−40 1.00000 B 0.664000 0.046071 ExxRL HhhHH 194.4 85.3 1592.412.143932 6.0904e−34 1.00000 N 0.122080 0.053562 YxxEN HhhHH 47.1 12.1158.4 10.435507 4.0653e−25 1.00000 N 0.297348 0.076699 ExxRE HhhHH 240.2130.3 1378.1 10.115517 3.7685e−24 1.00000 N 0.174298 0.094564 AxxTTCchHH 31.4 3.0 95.3 16.791123 1.7851e−23 1.00000 B 0.329486 0.031067DxxRR HhhHH 121.9 52.8 600.5 9.963409 2.2695e−23 1.00000 N 0.2029980.087883 AxxRR HhhHH 119.0 51.0 722.4 9.873794 5.5640e−23 1.00000 N0.164729 0.070617 DxxGK CccCH 31.4 3.2 84.3 16.156690 6.4849e−23 1.00000B 0.372479 0.037626 ExxRA HhhHH 216.7 115.4 1491.6 9.812480 8.0321e−231.00000 N 0.145280 0.077390 PxxGK CccCH 37.1 8.6 207.4 9.8932101.2460e−22 1.00000 N 0.178881 0.041644 YxxGR HhcCC 27.9 5.6 83.69.814050 4.2178e−22 1.00000 N 0.333732 0.066430 AxxER HhhHH 160.2 78.8960.0 9.579453 8.6052e−22 1.00000 N 0.166875 0.082033 CxxCW CecHH 10.10.0 32.8 49.128009 8.8894e−22 1.00000 B 0.307927 0.001280 QxxAA HhhHH119.9 52.6 1024.0 9.528485 1.5740e−21 1.00000 N 0.117090 0.051362 HxxNEHhhHH 36.8 9.1 122.0 9.582928 2.4752e−21 1.00000 N 0.301639 0.074219RxxMD HhhEC 17.1 0.6 44.2 22.238496 2.7644e−21 1.00000 B 0.3868780.012675 NxxCK EecCC 24.2 2.0 45.0 15.927613 6.0120e−21 1.00000 B0.537778 0.045091 AxxRA HhhHH 165.8 82.7 1804.6 9.359131 6.8374e−211.00000 N 0.091876 0.045813 ExxRQ HhhHH 149.6 73.1 886.5 9.3448418.1784e−21 1.00000 N 0.168754 0.082435 ExxAA HhhHC 52.1 16.1 214.09.306055 2.2237e−20 1.00000 N 0.243458 0.075445 PxxNI CeeCC 14.4 0.513.3 19.167577 1.9524e−19 1.00000 B 1.082707 0.034936 QxxEG HhhHC 34.98.9 104.9 9.070130 2.9112e−19 1.00000 N 0.332698 0.085314 SxxAA HhhHH78.9 30.6 960.7 8.862496 8.8792e−19 1.00000 N 0.082128 0.031889 AxxARHhhHH 118.4 54.8 1244.1 8.783439 1.4619e−18 1.00000 N 0.095169 0.044062AxxSQ HhhHC 32.8 8.4 98.7 8.827817 2.6401e−18 1.00000 N 0.3323200.084790 AxxEA HhhHH 188.2 103.4 2180.2 8.538938 1.0460e−17 1.00000 N0.086322 0.047445 GxxNS CchHH 25.9 3.1 66.8 13.347601 1.3878e−17 1.00000B 0.387725 0.045915 NxxPN HhcHH 25.0 5.6 53.4 8.621938 2.2460e−171.00000 N 0.468165 0.105585 SxxGN CccCH 16.7 1.1 22.8 15.3338503.2588e−17 1.00000 B 0.732456 0.047742 YxxNF CccCC 23.9 5.1 96.28.563062 3.8617e−17 1.00000 N 0.248441 0.052944 SxxVD CeeEE 71.1 28.4311.2 8.413504 4.5859e−17 1.00000 N 0.228470 0.091179 ExxLA HhhHH 172.994.5 1763.6 8.285516 9.1556e−17 1.00000 N 0.098038 0.053601 HxxQA HhhCH1.0 0.1 1.0 3.306715 1.0172e−16 1.00000 B 1.000000 0.083792 ExxAA HhhHH179.9 99.7 1794.4 8.266710 1.0592e−16 1.00000 N 0.100256 0.055555 TxxDKEeeEE 91.2 40.9 412.9 8.290419 1.1242e−16 1.00000 N 0.220877 0.099016RxxRE HhhHH 141.4 74.0 828.4 8.217981 1.7164e−16 1.00000 N 0.1706900.089275 VxxHE HhhHH 28.9 4.0 173.8 12.540326 2.2042e−16 1.00000 B0.166283 0.023172 KxxGA HhcCC 44.0 13.9 283.3 8.262977 2.2260e−161.00000 N 0.155312 0.049167 RxxGI HhcCC 41.0 12.7 265.2 8.1420276.3123e−16 1.00000 N 0.154600 0.047865 AxxRT HccCC 23.5 5.3 79.38.142951 1.1990e−15 1.00000 N 0.296343 0.067278 VxxGA HhcCC 33.4 9.3235.9 8.076537 1.2963e−15 1.00000 N 0.141585 0.039348 KxxGF HhcCC 37.311.3 204.8 7.969461 2.7196e−15 1.00000 N 0.182129 0.055082 AxxRD HhhHH77.3 33.4 420.4 7.903500 2.7836e−15 1.00000 N 0.183873 0.079560 CxxCHCccCC 24.7 5.9 98.0 8.021387 2.8947e−15 1.00000 N 0.252041 0.059844AxxAS HhhHH 77.3 33.1 862.3 7.834917 4.7308e−15 1.00000 N 0.0896440.038384 AxxAE HhhHH 133.4 70.4 1311.8 7.716222 9.6679e−15 1.00000 N0.101692 0.053677 SxxGL HhhCC 27.2 7.0 120.2 7.839361 1.0445e−14 1.00000N 0.226290 0.058491 ExxGL HhcCC 64.7 26.4 437.9 7.674219 1.8107e−141.00000 N 0.147751 0.060392 VxxKN EccCC 29.4 8.2 105.5 7.7475121.9363e−14 1.00000 N 0.278673 0.077267 LxxLH HhhHH 39.2 12.4 609.37.696374 2.1292e−14 1.00000 N 0.064336 0.020332 AxxRE HhhHH 138.9 75.7940.9 7.575524 2.8327e−14 1.00000 N 0.147625 0.080452 ExxLS HhhHH 102.250.1 839.3 7.584261 2.9242e−14 1.00000 N 0.121768 0.059728 ExxGA HhhCC41.1 13.7 243.7 7.613209 3.8832e−14 1.00000 N 0.168650 0.056268 KxxACEeeCC 18.1 1.8 44.0 12.344442 3.9683e−14 1.00000 B 0.411364 0.041254HxxKV HhhHH 33.0 9.8 164.9 7.631524 4.1038e−14 1.00000 N 0.2001210.059517 AxxAA HhhHC 61.6 25.0 435.1 7.547460 4.8688e−14 1.00000 N0.141577 0.057408 AxxGL HhhCC 41.1 13.8 280.1 7.540236 6.6990e−141.00000 N 0.146733 0.049246 SxxTT CchHH 22.4 3.0 85.8 11.5092297.9920e−14 1.00000 B 0.261072 0.034452 AxxRH HhhHH 52.1 19.9 294.87.480402 8.9042e−14 1.00000 N 0.176730 0.067458 RxxGL HhcCC 53.5 20.6336.0 7.465023 9.8050e−14 1.00000 N 0.159226 0.061435 CxxCH HhhHE 13.21.3 13.5 11.110583 1.4758e−13 1.00000 B 0.977778 0.094252 AxxAQ HhhHH79.5 36.2 761.4 7.381135 1.4828e−13 1.00000 N 0.104413 0.047510 LxxNVCchHH 25.9 4.5 77.5 10.453245 1.5252e−13 1.00000 B 0.334194 0.057583AxxQD HhhHH 65.9 28.4 324.1 7.377042 1.6844e−13 1.00000 N 0.2033320.087528 GxxGK CccCH 26.0 6.8 249.5 7.472893 1.6894e−13 1.00000 N0.104208 0.027222 MxxCT EecCC 8.0 0.1 11.6 20.815710 1.7845e−13 1.00000B 0.689655 0.012433 PxxAA HhhHH 66.0 27.9 816.2 7.342254 2.1476e−131.00000 N 0.080863 0.034173 NxxHQ HhhHH 21.3 5.1 62.2 7.4714132.2332e−13 1.00000 N 0.342444 0.082215 MxxSR HhhHC 19.9 2.5 52.111.260987 2.7264e−13 1.00000 B 0.381958 0.048106 KxxDG EccCC 71.2 31.9339.7 7.297480 2.9121e−13 1.00000 N 0.209597 0.094033 DxxRA HhhHH 112.558.9 823.5 7.256832 3.2587e−13 1.00000 N 0.136612 0.071469 DxxRN HhhHC24.5 6.5 74.9 7.380530 3.6042e−13 1.00000 N 0.327103 0.086891 AxxQAHhhHH 113.8 59.5 1177.6 7.223678 4.1184e−13 1.00000 N 0.096637 0.050530DxxSN HhhHH 31.0 9.4 133.5 7.288476 5.4139e−13 1.00000 N 0.2322100.070612 NxxRN HhhHH 33.2 10.6 140.1 7.236560 7.3844e−13 1.00000 N0.236974 0.075474 ExxLP HhhCC 31.6 9.7 176.5 7.229156 8.0852e−13 1.00000N 0.179037 0.054991 CxxNI EccCC 8.0 0.2 15.3 20.051595 8.1343e−131.00000 B 0.522876 0.010108 VxxTS CchHH 18.0 2.1 58.7 11.3245299.1748e−13 1.00000 B 0.306644 0.035000 CxxCH HhhHC 21.4 3.5 40.710.054804 9.3614e−13 1.00000 B 0.525799 0.085377 CxxCW CccHH 6.6 0.035.7 33.489514 1.1250e−12 1.00000 B 0.184874 0.001076 QxxMS CchHH 7.00.1 8.0 20.029061 1.3328e−12 1.00000 B 0.875000 0.014974 PxxLT HhhHH34.7 11.3 229.3 7.111345 1.7124e−12 1.00000 N 0.151330 0.049482 AxxQQHhhHH 73.7 34.2 442.5 7.033591 1.8980e−12 1.00000 N 0.166554 0.077271GxxAA HhhHH 53.5 21.4 1130.0 7.016140 2.4760e−12 1.00000 N 0.0473450.018914 AxxGR CccHH 15.6 1.4 64.8 12.259572 2.5530e−12 1.00000 B0.240741 0.021226 AxxDA HhhHH 99.9 51.3 1121.1 6.945769 3.1146e−121.00000 N 0.089109 0.045761 QxxGL CccCH 17.9 2.2 47.3 10.7290264.0680e−12 1.00000 B 0.378436 0.047294 SxxDS HhhHH 28.9 8.9 121.46.997453 4.4603e−12 1.00000 N 0.238056 0.072925 QxxND HhhHH 36.3 12.7151.8 6.922566 6.1794e−12 1.00000 N 0.239130 0.083607

TABLE 14 In Expected P-Value P-Value Observed Null Sequence StructureEpitopes in Epi In PDB Z-Score Upper Lower Distribution RatioProbability GxGxS CcChH 90.7 18.3 441.1 17.277824 2.7158e−66 1.00000 N0.205622 0.041517 GxGxT CcChH 82.9 19.3 472.3 14.775292 5.8901e−491.00000 N 0.175524 0.040888 AxKxT CcHhH 46.2 2.3 132.8 28.9733603.8354e−46 1.00000 B 0.347892 0.017570 SxKxT CcHhH 45.9 2.3 169.028.763578 1.0498e−44 1.00000 B 0.271598 0.013768 VxKxS CcHhH 34.5 1.5112.2 27.236570 1.7784e−36 1.00000 B 0.307487 0.013269 GxGxG CcChH 43.78.6 269.1 12.148832 2.3822e−33 1.00000 N 0.162393 0.032017 TxVxK EeEeE106.2 37.4 568.5 11.640466 3.4471e−31 1.00000 N 0.186807 0.065781 SxKxDCeEeE 66.9 19.0 237.4 11.470166 3.6870e−30 1.00000 N 0.281803 0.079926TxTxK CcCcH 29.5 1.8 56.2 20.951875 9.2706e−29 1.00000 B 0.5249110.032121 VxCxN EcCcC 28.9 2.1 67.3 19.011379 1.1251e−25 1.00000 B0.429421 0.030557 SxVxK CcCcH 25.8 1.9 101.1 17.528911 1.3538e−211.00000 B 0.255193 0.018747 GxTxS CcHhH 25.7 2.3 77.1 15.7005516.1084e−20 1.00000 B 0.333333 0.029715 QxGxT CcChH 22.7 1.9 40.415.608649 9.3613e−20 1.00000 B 0.561881 0.046230 DxAxK CcCcH 22.0 1.762.2 15.851300 4.4906e−19 1.00000 B 0.353698 0.027136 KxDxK EeEeE 78.231.5 395.3 8.663783 5.1313e−18 1.00000 N 0.197824 0.079765 SxTxV HcEeE67.5 26.5 339.7 8.277657 1.4600e−16 1.00000 N 0.198705 0.078155 SxTxNCcCcH 15.3 1.0 22.5 15.029372 3.7791e−16 1.00000 B 0.680000 0.042297QxPxS EeCcE 34.5 9.6 273.2 8.163922 6.2295e−16 1.00000 N 0.1262810.035226 QxKxG HhHhC 36.0 10.4 188.4 8.142734 7.1133e−16 1.00000 N0.191083 0.055388 KxVxC EeEcC 19.9 1.9 57.7 13.267711 2.7457e−15 1.00000B 0.344887 0.032977 NxAxK EeCcC 24.7 3.6 55.5 11.503434 4.7976e−151.00000 B 0.445045 0.064834 GxTxY CcEeE 52.6 19.4 391.0 7.7329011.3037e−14 1.00000 N 0.134527 0.049610 RxKxG EcCcC 27.1 7.1 109.27.781732 1.6320e−14 1.00000 N 0.248168 0.064822 AxGxR HcCcC 36.6 11.5170.4 7.680274 2.5874e−14 1.00000 N 0.214789 0.067340 SxGxG EeCcC 26.36.7 281.3 7.709803 2.8760e−14 1.00000 N 0.093494 0.023647 NxGxT CcChH20.3 2.4 51.0 11.698574 5.4820e−14 1.00000 B 0.398039 0.047969 PxWxICeEcC 12.3 0.3 9.3 15.817318 1.4860e−13 1.00000 B 1.322581 0.035840SxGxG CcCcH 25.0 3.9 151.4 10.870832 1.7440e−13 1.00000 B 0.1651250.025597 TxMxF CcCcC 18.4 2.0 52.3 11.772241 2.9763e−13 1.00000 B0.351816 0.038525 GxSxE CcChH 87.9 42.3 619.0 7.264315 3.3686e−131.00000 N 0.142003 0.068333 RxRxG EcCcC 21.8 5.3 79.6 7.3902633.8620e−13 1.00000 N 0.273869 0.066905 CxAxI CcCcC 15.6 1.3 50.112.992225 4.0316e−13 1.00000 B 0.311377 0.024970 RxSxT EeCcC 21.8 3.083.5 10.987197 5.0613e−13 1.00000 B 0.261078 0.036272 QxNxQ EeCcC 19.32.7 36.1 10.437162 9.0830e−13 1.00000 B 0.534626 0.075549 AxGxT HcCcC38.3 13.1 237.7 7.177890 9.9181e−13 1.00000 N 0.161127 0.054993 CxGxHChHhH 9.4 0.3 13.6 16.130102 1.8371e−12 1.00000 B 0.691176 0.023847QxGxC CcCcH 12.3 0.8 22.2 12.974678 2.2038e−12 1.00000 B 0.5540540.036647 QxNxN CeCcC 17.6 2.4 31.2 10.223071 5.2458e−12 1.00000 B0.564103 0.076790 NxKxD CeEeE 36.1 12.5 155.1 6.939188 5.5327e−121.00000 N 0.232753 0.080856 QxPxR HcHhH 18.2 2.4 55.2 10.4893307.0720e−12 1.00000 B 0.329710 0.043075 YxSxR HhCcC 18.3 2.5 49.810.332758 8.5782e−12 1.00000 B 0.367470 0.049592 MxIxE CcHhH 20.5 5.1117.7 6.943104 9.2565e−12 1.00000 N 0.174172 0.043553 GxTxW EeCcC 9.10.4 14.3 14.427172 1.2572e−11 1.00000 B 0.636364 0.026262 GxExF CcCeE20.1 5.0 116.8 6.848623 1.7824e−11 1.00000 N 0.172089 0.043222 DxNxECcChH 25.1 7.3 128.5 6.781685 2.1820e−11 1.00000 N 0.195331 0.056827VxKxC CcHhH 10.0 0.4 62.5 14.474398 2.4703e−11 1.00000 B 0.1600000.007030 HxNxR EeEeE 10.4 0.5 41.7 14.375158 2.5174e−11 1.00000 B0.249400 0.011550 CxNxQ CcCcC 20.1 3.1 82.3 9.762451 2.6118e−11 1.00000B 0.244228 0.038133 AxVxR CcChH 10.8 0.6 30.0 13.215029 5.4998e−111.00000 B 0.360000 0.020240 KxGxT CcCcC 72.0 34.9 523.7 6.5089956.7535e−11 1.00000 N 0.137483 0.066578 DxDxT CcCcE 20.6 5.5 97.66.635209 7.0133e−11 1.00000 N 0.211066 0.056280 ExGxS EcCcC 22.8 4.3107.0 9.131379 8.1828e−11 1.00000 B 0.213084 0.040032 PxHxA CcHhH 13.81.3 42.8 11.025072 8.4644e−11 1.00000 B 0.322430 0.030883 GxLxL CcCcH18.9 2.8 110.4 9.756476 8.9145e−11 1.00000 B 0.171196 0.025321 CxGxIEcCcC 7.0 0.2 19.8 17.719130 9.6238e−11 1.00000 B 0.353535 0.007605QxQxN CcCeC 16.7 2.5 32.4 9.345434 1.2978e−10 1.00000 B 0.5154320.077204 NxGxM EcCcH 8.1 0.3 12.3 13.702397 1.4709e−10 1.00000 B0.658537 0.026861 MxLxT EeCcC 13.0 1.2 48.2 10.653411 2.0738e−10 1.00000B 0.269710 0.025913 DxNxY CcCcE 20.3 5.6 84.7 6.441134 2.4504e−101.00000 N 0.239669 0.065956 TxKxT CcHhH 14.0 1.5 79.3 10.2470233.4869e−10 1.00000 B 0.176545 0.019088 YxHxC CcCcC 7.0 0.3 8.0 13.1077024.1509e−10 1.00000 B 0.875000 0.034088 DxPxY CcCcC 26.5 8.6 158.06.299163 4.5765e−10 1.00000 N 0.167722 0.054230 DxGxG CcCcC 70.9 35.3709.9 6.151718 6.5827e−10 1.00000 N 0.099873 0.049697 NxTxN HhChH 18.43.3 47.3 8.623012 6.9892e−10 1.00000 B 0.389006 0.069712 PxSxK CcCcH11.8 1.0 49.0 10.999112 7.9644e−10 1.00000 B 0.240816 0.020131 AxIxRCcCcH 10.8 0.8 37.9 11.351590 1.0590e−09 1.00000 B 0.284960 0.020941CxGxS CcCcC 25.9 8.3 343.1 6.157692 1.0995e−09 1.00000 N 0.0754880.024300 TxPxG EcCcC 38.8 15.5 285.9 6.068337 1.4435e−09 1.00000 N0.135712 0.054349 GxLxH CcCeE 13.8 1.7 43.6 9.388972 2.2415e−09 1.00000B 0.316514 0.039512 NxGxH EcCcE 11.7 1.1 56.8 10.371446 2.9851e−091.00000 B 0.205986 0.018848 GxVxK CcCcH 18.9 3.5 160.1 8.4036783.7537e−09 1.00000 B 0.118051 0.021569 DxLxA HhCcH 14.8 2.1 66.29.025764 3.9660e−09 1.00000 B 0.223565 0.031075 VxKxA CcHhH 16.4 2.5126.8 8.768982 4.4341e−09 1.00000 B 0.129338 0.020086 TxAxK CcCcH 11.11.1 35.8 9.811276 4.5969e−09 1.00000 B 0.310056 0.030060 VxPxY EcCcC20.4 4.2 105.4 8.032775 4.7842e−09 1.00000 B 0.193548 0.040079 NxGxMHcCcH 6.6 0.2 7.8 13.426233 5.8155e−09 1.00000 B 0.846154 0.029725 KxNxYEeCcC 10.3 1.1 16.6 9.184465 8.7789e−09 1.00000 B 0.620482 0.064951NxFxV HcCcH 6.3 0.2 8.0 12.666549 1.2366e−08 1.00000 B 0.787500 0.029519GxSxL EeEcC 7.0 0.3 22.8 12.325790 1.2828e−08 1.00000 B 0.3070180.013134 CxSxW CeChH 4.9 0.0 37.1 23.296904 1.3101e−08 1.00000 B0.132075 0.001173 LxPxE CcChH 21.8 7.1 105.6 5.746143 1.4179e−08 1.00000N 0.206439 0.066814 CxQxT CcEeE 11.5 1.3 36.0 9.258328 1.4559e−081.00000 B 0.319444 0.035176 SxSxN CcChH 18.1 5.3 85.1 5.7481421.6594e−08 1.00000 N 0.212691 0.062200 QxRxY CcCcH 7.8 0.5 10.110.639154 1.7285e−08 1.00000 B 0.772277 0.049077 CxAxH ChHhH 9.0 0.737.3 10.163442 1.9366e−08 1.00000 B 0.241287 0.018291 NxGxS CcChH 14.82.4 58.5 8.220381 2.1270e−08 1.00000 B 0.252991 0.040678 LxFxI CcEeE10.2 0.9 64.5 9.774234 2.1939e−08 1.00000 B 0.158140 0.014191 NxQxQCcCcC 26.5 9.7 142.4 5.615982 2.5284e−08 1.00000 N 0.186096 0.067789LxVxY CcCeE 9.4 0.8 32.2 9.906317 3.0929e−08 1.00000 B 0.291925 0.024115AxIxR CcChH 8.3 0.5 27.6 10.629105 3.0952e−08 1.00000 B 0.3007250.019683 PxVxK CcCcH 13.5 1.9 84.7 8.381770 4.1718e−08 1.00000 B0.159386 0.022965 GxWxT CcEcC 9.5 0.9 21.6 9.360565 4.2598e−08 1.00000 B0.439815 0.040902 SxGxN HcCcC 25.3 9.2 143.6 5.513759 4.5713e−08 1.00000N 0.176184 0.063763 KxWxE CcHhH 18.1 5.5 80.6 5.559426 4.6811e−081.00000 N 0.224566 0.068327 HxGxI EcCcE 8.9 0.7 23.9 9.773384 4.7466e−081.00000 B 0.372385 0.030209 GxDxS CcChH 35.0 14.7 228.2 5.4622924.9765e−08 1.00000 N 0.153374 0.064532 DxGxT CcChH 14.4 2.3 86.88.053573 5.0224e−08 1.00000 B 0.165899 0.026657 ExCxL EcCcC 7.0 0.4 14.610.508475 5.2940e−08 1.00000 B 0.479452 0.027746 QxLxR HhCeE 6.0 0.2 5.512.663540 5.3355e−08 1.00000 B 1.090909 0.033159

TABLE 15 In Expected P-Value P-Value Observed Null Sequence StructureEpitopes in Epi In PDB Z-Score Upper Lower Distribution RatioProbability GxGKS CcCHH 76.8 5.7 258.3 30.117905  8.1947e−197 1.00000 N0.297329 0.022063 GxGKT CcCHH 71.0 7.8 333.8 22.901721  1.4036e−1141.00000 N 0.212702 0.023362 AxKTT CcHHH 30.3 0.5 54.5 43.7615081.2949e−47 1.00000 B 0.555963 0.008600 DxAGK CcCCH 22.0 0.2 41.347.793028 8.6206e−40 1.00000 B 0.532688 0.005059 TxVDK EeEEE 90.0 25.8396.0 13.077707 8.3835e−39 1.00000 N 0.227273 0.065121 TxTGK CcCCH 29.51.0 40.8 28.771739 5.4168e−38 1.00000 B 0.723039 0.024647 SxKVD CeEEE63.6 15.5 231.4 12.646853 3.0755e−36 1.00000 N 0.274849 0.066994 SxVGKCcCCH 23.3 0.5 68.7 32.580886 2.7209e−32 1.00000 B 0.339156 0.007184KxDKK EeEEE 72.2 22.8 341.6 10.701700 1.5998e−26 1.00000 N 0.2113580.066796 VxCKN EcCCC 27.9 1.9 55.4 19.445212 3.8832e−26 1.00000 B0.503610 0.033503 SxKTT CcHHH 19.7 0.5 60.3 28.032814 5.4204e−26 1.00000B 0.326700 0.007862 GxTNS CcHHH 24.7 1.5 42.7 19.617101 6.3209e−251.00000 B 0.578454 0.034045 NxACK EeCCC 24.2 1.7 45.0 17.6233509.2961e−23 1.00000 B 0.537778 0.037658 SxTKV HcEEE 63.7 20.9 316.49.703558 4.3917e−22 1.00000 N 0.201327 0.065941 AxIGR CcCCH 9.7 0.0 16.757.885963 6.0124e−22 1.00000 B 0.580838 0.001675 NxGKT CcCHH 19.3 0.937.9 20.057542 9.8345e−22 1.00000 B 0.509235 0.022811 SxKST CcHHH 19.20.8 76.4 21.405193 1.4297e−21 1.00000 B 0.251309 0.009821 QxGKT CcCHH18.3 1.0 26.2 17.901767 1.8566e−20 1.00000 B 0.698473 0.037136 TxNIGEeCCC 15.3 0.4 13.6 20.474271 6.1792e−20 1.00000 B 1.125000 0.031424VxKSS CcHHH 15.0 0.4 39.5 22.555376 6.7674e−20 1.00000 B 0.3797470.010689 VxKTS CcHHH 15.5 0.4 39.6 22.701630 7.4836e−20 1.00000 B0.391414 0.011232 GxGLG CcCHH 13.3 0.3 18.5 23.108179 1.2849e−19 1.00000B 0.718919 0.017353 CxAGI CcCCC 10.8 0.1 24.5 35.991458 1.9508e−191.00000 B 0.440816 0.003628 SxTGN CcCCH 15.2 0.5 13.6 18.9790564.1390e−19 1.00000 B 1.117647 0.036383 CxGNI EcCCC 7.0 0.0 12.065.388018 5.6234e−19 1.00000 B 0.583333 0.000953 AxGRT HcCCC 20.9 1.839.1 14.657288 6.6192e−18 1.00000 B 0.534527 0.045587 NxLFV CcCEE 2.00.1 2.0 6.867619 1.7331e−17 1.00000 B 1.000000 0.040680 RxTDV CcCCH 3.00.1 2.0 5.982392 2.2260e−17 1.00000 B 1.500000 0.052925 VxKSA CcHHH 12.40.3 50.8 23.682682 2.9348e−17 1.00000 B 0.244094 0.005196 YxSGR HhCCC18.3 1.4 32.2 14.636474 6.2283e−17 1.00000 B 0.568323 0.043307 QxTYSCcCEE 1.7 0.1 1.0 3.973058 1.0441e−16 1.00000 B 1.700000 0.059576 HxASVEeEEC 3.0 0.1 1.0 4.165174 1.0497e−16 1.00000 B 3.000000 0.054500 KxVHAHcHHH 1.0 0.0 1.0 4.757945 1.0633e−16 1.00000 B 1.000000 0.042305 NxPKCCcCCC 1.0 0.0 1.0 4.879347 1.0655e−16 1.00000 B 1.000000 0.040310 SxNTYEhHHH 1.0 0.0 1.0 5.471530 1.0743e−16 1.00000 B 1.000000 0.032323 DxRFVCcCCE 1.0 0.0 1.0 5.693042 1.0770e−16 1.00000 B 1.000000 0.029931 GxRDNCcEEE 1.0 0.0 1.0 7.131346 1.0888e−16 1.00000 B 1.000000 0.019284 PxYASCeEEC 1.0 0.0 1.0 7.330621 1.0899e−16 1.00000 B 1.000000 0.018269 NxKVDCeEEE 34.1 9.4 138.3 8.361157 1.2840e−16 1.00000 N 0.246565 0.067811AxIGR CcCHH 7.3 0.0 20.2 44.635958 3.9779e−16 1.00000 B 0.3613860.001316 KxVAC EeECC 17.6 1.4 42.0 14.190491 2.2162e−15 1.00000 B0.419048 0.032245 RxSET EeCCC 13.5 0.6 32.5 16.822086 4.6601e−15 1.00000B 0.415385 0.018436 PxSGK CcCCH 11.0 0.3 33.9 18.247326 2.6524e−141.00000 B 0.324484 0.010162 QxKEG HhHHC 24.5 3.8 61.1 10.9337364.3327e−14 1.00000 B 0.400982 0.062470 QxNTN CeCCC 17.4 1.8 28.111.884158 5.1239e−14 1.00000 B 0.619217 0.065309 CxGDS CcCCC 15.2 0.9207.8 14.779991 6.0370e−14 1.00000 B 0.073147 0.004503 GxTDW EeCCC 9.10.3 9.4 16.644901 6.1205e−14 1.00000 B 0.968085 0.030755 LxNIC CcCCC 6.00.0 9.0 35.855552 7.2836e−14 1.00000 B 0.666667 0.003092 MxLCT EeCCC 8.00.1 11.1 21.256674 1.0538e−13 1.00000 B 0.720721 0.012478 GxLAH CcCEE12.8 0.6 32.0 15.555407 1.0819e−13 1.00000 B 0.400000 0.019525 PxWNICeECC 12.3 0.3 9.3 16.048196 1.1558e−13 1.00000 B 1.322581 0.034852TxCGV CcEEE 5.3 0.0 5.0 42.614482 1.5607e−13 1.00000 B 1.060000 0.002746MxTFK HcCCC 9.5 0.3 10.7 17.091968 1.6743e−13 1.00000 B 0.8878500.027865 TxKTF CcHHH 8.0 0.1 10.8 20.437125 1.6991e−13 1.00000 B0.740741 0.013854 AxVGR CcCHH 8.3 0.1 21.0 23.322674 1.9270e−13 1.00000B 0.395238 0.005887 GxICR CcCCH 5.0 0.0 10.7 51.742841 1.9290e−131.00000 B 0.467290 0.000870 RxLGR CcHHH 7.0 0.1 7.5 21.419092 3.3098e−131.00000 B 0.933333 0.014013 QxPNR HcHHH 17.2 1.8 47.4 11.8638884.3286e−13 1.00000 B 0.362869 0.037114 AxKNG CcCCC 22.6 3.5 59.610.545781 4.7755e−13 1.00000 B 0.379195 0.058531 QxIMS CcHHH 5.0 0.0 5.036.728563 6.8672e−13 1.00000 B 1.000000 0.003693 GxVGK CcCCH 14.6 1.0107.2 13.322350 1.6400e−12 1.00000 B 0.136194 0.009752 PxVGK CcCCH 12.00.6 51.9 14.216855 1.7503e−12 1.00000 B 0.231214 0.012444 SxSGK CcCCH7.7 0.1 25.4 24.456096 1.8641e−12 1.00000 B 0.303150 0.003820 NxGKSCcCHH 12.5 0.7 33.0 13.743835 2.1757e−12 1.00000 B 0.378788 0.022670CxGCH ChHHH 9.4 0.3 12.7 15.666301 2.1818e−12 1.00000 B 0.7401570.027045 QxVGK CcCCH 5.0 0.0 10.0 39.581665 2.5288e−12 1.00000 B0.500000 0.001588 SxGIG CcCCH 5.9 0.0 23.8 38.855311 3.3879e−12 1.00000B 0.247899 0.000962 DxGVG CcCCC 17.9 2.1 85.4 11.043562 5.6770e−121.00000 B 0.209602 0.024576 GxTVE CeEEE 19.5 2.9 45.9 10.0913626.2818e−12 1.00000 B 0.424837 0.062984 SxGVG CcCCH 7.7 0.1 25.522.270296 6.6754e−12 1.00000 B 0.301961 0.004568 HxLAV EeEEE 5.0 0.010.7 35.885329 7.3464e−12 1.00000 B 0.467290 0.001804 VxKSN CcHHH 6.30.1 11.0 25.731736 7.6458e−12 1.00000 B 0.572727 0.005376 TxAGK CcCCH9.1 0.3 20.0 15.689912 8.4739e−12 1.00000 B 0.455000 0.015917 DxGKTCcCHH 10.5 0.5 43.6 14.602866 2.0076e−11 1.00000 B 0.240826 0.010926NxGYH EcCCE 11.7 0.7 37.8 13.208215 2.2537e−11 1.00000 B 0.3095240.018678 PxGPP CcCCC 18.4 2.7 56.0 9.854107 3.9241e−11 1.00000 B0.328571 0.047758 CxSCW CeCHH 4.9 0.0 28.3 47.000314 4.6279e−11 1.00000B 0.173145 0.000383 RxRPF EeCCC 7.5 0.2 7.0 14.155047 4.9950e−11 1.00000B 1.071429 0.033757 NxTPN HhCHH 18.4 2.8 46.3 9.571722 5.2061e−111.00000 B 0.397408 0.060928 QxSGK CcCCH 8.2 0.3 19.9 15.9153185.6650e−11 1.00000 B 0.412060 0.012692 TxKFY CcCEC 8.0 0.3 9.5 13.3157505.8205e−11 1.00000 B 0.842105 0.036110 SxGNT CcCHH 8.0 0.3 12.713.715844 1.4847e−10 1.00000 B 0.629921 0.025318 CxSCW CcCHH 4.6 0.033.7 45.330484 1.5256e−10 1.00000 B 0.136499 0.000304 TxKTT CcHHH 10.00.5 49.2 12.893235 1.5785e−10 1.00000 B 0.203252 0.011055 NxGLG CcCHH8.0 0.1 6.1 16.108152 1.6728e−10 1.00000 B 1.311475 0.022969 YxTMS CcCEE11.7 0.8 42.8 11.916591 1.8497e−10 1.00000 B 0.273364 0.019773 FxRILCcCCC 8.8 0.4 17.8 14.255412 1.9039e−10 1.00000 B 0.494382 0.020107QxGSC CcCCH 7.5 0.2 20.2 17.095416 2.0620e−10 1.00000 B 0.3712870.009148 IxNYT EcCCC 9.6 0.4 48.0 13.897106 2.2756e−10 1.00000 B0.200000 0.009137 KxVNT CcEEE 10.5 0.6 64.8 12.844695 2.6279e−10 1.00000B 0.162037 0.009254 PxMNR CcCCH 7.9 0.3 9.0 13.625788 2.6767e−10 1.00000B 0.877778 0.035649 FxYSQ CcCCC 8.2 0.5 8.0 10.849473 2.6899e−10 1.00000B 1.025000 0.063638 LxVGM CeEEE 3.5 0.0 7.0 82.843231 2.8933e−10 1.00000B 0.500000 0.000255 AxGKT CcCHH 17.5 2.5 101.1 9.616395 2.9615e−101.00000 B 0.173096 0.024688 GxTGK CcCCH 8.0 0.3 35.0 14.6755353.1693e−10 1.00000 B 0.228571 0.007972 KxNNY EeCCC 9.2 0.5 8.5 11.3733923.3783e−10 1.00000 B 1.082353 0.061659 YxHFC CcCCC 6.0 0.2 6.0 13.9559007.1245e−10 1.00000 B 1.000000 0.029885 QxQCG CcCCC 8.4 0.3 27.113.832080 7.5500e−10 1.00000 B 0.309963 0.012679 QxRGY CcCCH 7.8 0.3 9.113.087877 7.7131e−10 1.00000 B 0.857143 0.037102

TABLE 16 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySGxxT CChhH 50.1 5.4 204.2 19.480512 5.5365e−83 1.00000 N 0.2453480.026478 YHxxN HHhhH 50.5 6.5 81.8 18.012634 3.0622e−71 1.00000 N0.617359 0.079280 NKxxL ECccC 51.0 6.6 166.5 17.606843 3.5567e−681.00000 N 0.306306 0.039743 AGxxT CChhH 48.1 6.2 185.3 17.1107412.0133e−64 1.00000 N 0.259579 0.033476 HExxH HHhhH 53.2 3.1 231.028.733287 2.3099e−48 1.00000 B 0.230303 0.013348 ACxxG CCccC 42.2 6.3122.4 14.733487 3.9997e−48 1.00000 N 0.344771 0.051214 VIxxW CChhH 27.80.4 36.0 41.212009 5.6053e−45 1.00000 B 0.772222 0.012391 TGxxK CCccH38.5 6.6 151.0 12.684841 4.4532e−36 1.00000 N 0.254967 0.043773 GVxxSCCchH 55.7 13.3 271.0 11.955548 1.6382e−32 1.00000 N 0.205535 0.048905QDxxG HHhhC 41.1 8.7 96.0 11.495017 5.3755e−30 1.00000 N 0.4281250.090888 EExxR HHhhH 314.5 174.2 1989.2 11.126843 7.2386e−29 1.00000 N0.158104 0.087580 NFxxL HHhhH 42.8 5.0 298.3 17.058911 3.0896e−261.00000 B 0.143480 0.016745 VGxxS CChhH 33.7 3.0 132.7 17.9808652.6985e−25 1.00000 B 0.253956 0.022495 LSxxE CChhH 117.4 48.7 851.810.137582 3.9929e−24 1.00000 N 0.137826 0.057178 FPxxL HHhhH 39.1 9.1187.5 10.217915 4.6988e−24 1.00000 N 0.208533 0.048396 GFxxS CChhH 27.02.0 67.8 18.155159 5.3814e−24 1.00000 B 0.398230 0.028894 SGxxK CCccH36.9 8.3 196.7 10.104654 1.5766e−23 1.00000 N 0.187595 0.042407 EAxxAHHhhH 202.1 104.3 2020.6  9.828707 6.9670e−23 1.00000 N 0.1000200.051634 RRxxE HHhhH 190.5 98.6 1055.7  9.717855 2.1236e−22 1.00000 N0.180449 0.093412 LSxxY HHhhH 44.5 11.7 344.0  9.754079 3.7941e−221.00000 N 0.129360 0.034022 GLxxW EEccC 12.6 0.2 19.4 30.3247685.5134e−21 1.00000 B 0.649485 0.008738 TKxxK EEeeE 96.0 39.8 398.3 9.392073 6.4809e−21 1.00000 N 0.241024 0.099903 DExxR HHhhH 151.9 74.7886.6  9.330064 9.3406e−21 1.00000 N 0.171329 0.084280 AAxxA HHhhH 198.7105.9 3428.0  9.159010 4.1321e−20 1.00000 N 0.057964 0.030896 MNxxECChhH 44.6 13.0 167.5  9.123343 1.3666e−19 1.00000 N 0.266269 0.077633EGxxY ECccC 26.9 5.8 66.1  9.140516 2.2564e−19 1.00000 N 0.4069590.088175 LTxxE CChhH 100.6 43.5 866.0  8.873080 7.1316e−19 1.00000 N0.116166 0.050279 SKxxH HHhhH 34.0 8.8 105.4  8.902407 1.3189e−181.00000 N 0.322581 0.083153 EExxA HHhhH 231.4 135.1 1569.7  8.6638873.3802e−18 1.00000 N 0.147417 0.086081 STxxD CEeeE 70.3 27.5 272.3 8.618319 8.1370e−18 1.00000 N 0.258171 0.100879 VSxxE CChhH 56.4 19.6340.2  8.573591 1.3696e−17 1.00000 N 0.165785 0.057539 ARxxA HHhhH 122.158.7 1454.9  8.445356 2.6748e−17 1.00000 N 0.083923 0.040353 NYxxQ HHhhH29.9 7.3 161.4  8.557089 2.9366e−17 1.00000 N 0.185254 0.045252 AAxxGHHhhC 61.5 22.3 619.8  8.471116 3.0525e−17 1.00000 N 0.099226 0.035912PTxxI CEecC 14.3 0.7 18.8 16.909102 3.0897e−17 1.00000 B 0.7606380.035827 AAxxR HHhhH 129.8 64.3 1242.9  8.387023 4.2884e−17 1.00000 N0.104433 0.051739 GTxxT CCchH 27.9 6.6 168.1  8.420003 1.0007e−161.00000 N 0.165973 0.039491 VVxxR CCeeC 1.0 0.1 1.0  3.359317 1.0199e−161.00000 B 1.000000 0.081400 QQxxY HChhH 1.0 0.1 1.0  3.385522 1.0211e−161.00000 B 1.000000 0.080245 TQxxK CCccH 16.3 1.3 19.9 13.7886931.7270e−16 1.00000 B 0.819095 0.063780 AAxxQ HHhhH 100.7 46.6 848.8 8.140927 3.6432e−16 1.00000 N 0.118638 0.054957 ERxxM HHhhE 17.3 1.236.5 14.665548 4.8047e−16 1.00000 B 0.473973 0.034006 LSxxQ CChhH 60.822.9 428.9  8.130612 5.1480e−16 1.00000 N 0.141758 0.053451 AExxR HHhhH179.1 100.8 1506.8  8.070792 5.3200e−16 1.00000 N 0.118861 0.066910PExxR HHhhH 110.7 53.8 655.7  8.086699 5.4810e−16 1.00000 N 0.1688270.082123 RExxL HHhhH 112.2 54.5 836.4  8.083483 5.5774e−16 1.00000 N0.134146 0.065161 VAxxN ECccC 25.5 6.1 95.8  8.160134 9.3058e−16 1.00000N 0.266180 0.063248 NExxR HHhhH 68.6 27.9 378.6  7.995600 1.4251e−151.00000 N 0.181194 0.073776 RExxR HHhhH 155.0 85.2 968.1  7.9213361.8513e−15 1.00000 N 0.160107 0.087988 SAxxG CCccH 18.0 1.4 74.614.080334 3.0822e−15 1.00000 B 0.241287 0.018959 QFxxN CEccC 17.6 1.632.4 13.170193 6.2448e−15 1.00000 B 0.543210 0.048103 GHxxL CHhhC 13.20.8 17.8 14.597369 6.8060e−15 1.00000 B 0.741573 0.042626 ISxxT CChhH29.2 5.0 113.2 11.136582 6.9787e−15 1.00000 B 0.257951 0.043782 PVxxAHHhhH 42.9 14.1 430.6  7.802016 8.8311e−15 1.00000 N 0.099628 0.032730PGxxE CChhH 48.5 17.5 230.5  7.724590 1.4791e−14 1.00000 N 0.2104120.075770 ASxxT HCccC 23.5 5.6 109.1  7.765462 2.2008e−14 1.00000 N0.215399 0.051334 KNxxC EEecC 16.4 1.3 42.0 13.547220 2.8206e−14 1.00000B 0.390476 0.030577 CQxxS CCccC 22.8 5.3 160.0  7.735656 2.8522e−141.00000 N 0.142500 0.033098 QTxxR HChhH 18.2 1.8 48.4 12.6421802.9192e−14 1.00000 B 0.376033 0.036274 NQxxN HHchH 21.5 5.1 47.3 7.729667 3.3269e−14 1.00000 N 0.454545 0.107054 FRxxD HHhhC 17.5 1.4102.5 13.730817 3.4864e−14 1.00000 B 0.170732 0.013607 AAxxE HHhhH 158.989.7 1585.3  7.528216 3.8940e−14 1.00000 N 0.100233 0.056558 PExxA HHhhH127.9 68.2 958.9  7.506229 4.9065e−14 1.00000 N 0.133382 0.071091 RExxAHHhhH 122.1 64.6 824.6  7.452817 7.4518e−14 1.00000 N 0.148072 0.078335QTxxT CCchH 19.0 2.3 38.5 11.408119 7.7838e−14 1.00000 B 0.4935060.059291 PExxN HHhhH 42.6 15.0 197.4  7.430722 1.4792e−13 1.00000 N0.215805 0.075812 PGxxA CChhH 28.5 8.0 157.5  7.445140 1.8844e−131.00000 N 0.180952 0.050747 AQxxS HHhhH 50.4 19.0 360.1  7.3811351.8871e−13 1.00000 N 0.139961 0.052899 AExxQ HHhhH 100.1 50.3 642.7 7.316766 2.1891e−13 1.00000 N 0.155749 0.078242 EDxxY HHhhH 34.2 10.8168.1  7.391077 2.3540e−13 1.00000 N 0.203450 0.063963 LPxxV CChhH 31.79.5 328.1  7.313760 4.3680e−13 1.00000 N 0.096617 0.028935 GSxxT CCchH21.7 5.2 117.5  7.361159 4.7484e−13 1.00000 N 0.184681 0.044560 GGxxKCCccH 24.6 6.4 146.1  7.326094 5.2243e−13 1.00000 N 0.168378 0.044029QAxxD HHhhH 99.7 50.5 702.9  7.189078 5.5537e−13 1.00000 N 0.1418410.071827 MNxxD CChhH 22.2 5.6 69.2  7.324761 6.0496e−13 1.00000 N0.320809 0.080818 AExxA HHhhH 177.1 105.6 2016.0  7.144690 6.4810e−131.00000 N 0.087847 0.052392 CGxxW CEchH 10.4 0.3 41.6 17.5626146.5688e−13 1.00000 B 0.250000 0.007964 AExxS HHhhH 69.0 30.7 525.3 7.131241 9.7365e−13 1.00000 N 0.131354 0.058394 LAxxE HHhhH 111.2 58.31261.6  7.088647 1.0966e−12 1.00000 N 0.088142 0.046234 YQxxL HHhhH 40.113.9 386.6  7.155977 1.1141e−12 1.00000 N 0.103725 0.035961 GSxxS CCchH23.4 6.1 129.5  7.214135 1.2252e−12 1.00000 N 0.180695 0.046800 RSxxECChhH 37.0 12.6 179.8  7.134674 1.3888e−12 1.00000 N 0.205784 0.070013PExxT HHhhH 42.2 15.3 228.7  7.116551 1.4320e−12 1.00000 N 0.1845210.066926 RIxxN HHhhH 31.3 9.7 211.7  7.132289 1.6125e−12 1.00000 N0.147851 0.045594 ALxxE HHhhH 108.9 57.0 1224.1  7.032913 1.6407e−121.00000 N 0.088963 0.046595 STxxR HHhhH 44.8 16.8 265.4  7.0688101.9236e−12 1.00000 N 0.168802 0.063213 SWxxG EEccC 20.9 5.0 179.2 7.166893 1.9472e−12 1.00000 N 0.116629 0.028121 LGxxI CCeeE 20.7 2.8133.5 10.850496 2.8269e−12 1.00000 B 0.155056 0.020856 NVxxK EEccC 25.35.0 66.0  9.489538 2.9209e−12 1.00000 B 0.383333 0.075233 PAxxA HHhhH81.8 39.3 821.2  6.958559 3.0611e−12 1.00000 N 0.099610 0.047803 DAxxAHHhhH 128.3 71.5 1234.0  6.928395 3.2679e−12 1.00000 N 0.103971 0.057905WGxxC ECccC 21.1 3.0 152.1 10.567647 3.5349e−12 1.00000 B 0.1387250.019687 ISxxE CChhH 45.1 17.1 314.7  6.975012 3.6776e−12 1.00000 N0.143311 0.054250 RRxxA HHhhH 86.1 42.7 559.3  6.903535 4.4287e−121.00000 N 0.153942 0.076400 EQxxA HHhhH 117.1 64.1 862.2  6.8773304.7983e−12 1.00000 N 0.135815 0.074365 HGxxT CChhH 15.0 1.4 57.611.717492 5.1305e−12 1.00000 B 0.260417 0.024021 ANxxN HHhhH 26.8 7.9128.3  6.978653 5.4345e−12 1.00000 N 0.208885 0.061203 ARxxQ HHhhH 63.928.5 473.6  6.834976 8.0075e−12 1.00000 N 0.134924 0.060212 AQxxA HHhhH97.0 50.1 1116.6  6.788691 9.3146e−12 1.00000 N 0.086871 0.044831

TABLE 17 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityNKxDL ECcCC 51.0 4.4 116.2 22.740877 5.5464e−41 1.00000 B 0.4388980.037599 AGxTT CChHH 30.4 0.9 60.4 31.071504 1.5187e−38 1.00000 B0.503311 0.015139 TKxDK EEeEE 87.3 25.2 364.3 12.810007 2.7096e−371.00000 N 0.239638 0.069249 GVxKS CCcHH 35.9 1.9 116.9 24.8136737.8566e−35 1.00000 B 0.307100 0.016320 STxVD CEeEE 66.1 17.9 259.011.784220 9.9807e−32 1.00000 N 0.255212 0.069278 GFxNS CChHH 25.7 1.343.2 21.484488 2.0443e−27 1.00000 B 0.594907 0.030734 TGxGK CCcCH 33.62.8 111.4 18.471969 3.4400e−26 1.00000 B 0.301616 0.025536 SGxGK CCcCH32.6 2.9 157.9 17.436658 6.0866e−24 1.00000 B 0.206460 0.018664 KVxKKEEeEE 71.2 24.3 349.6  9.858861 8.8905e−23 1.00000 N 0.203661 0.069538NVxCK EEcCC 24.2 1.7 45.0 17.590163 1.0058e−22 1.00000 B 0.5377780.037786 TQxGK CCcCH 16.3 0.7 16.3 19.157024 2.0483e−22 1.00000 B1.000000 0.042526 VGxSS CChHH 15.0 0.4 36.0 24.399792 5.2733e−21 1.00000B 0.416667 0.010097 AGxGR CCcHH 13.2 0.2 54.5 30.666714 5.2900e−211.00000 B 0.242202 0.003318 QTxKT CCcHH 15.3 0.6 18.2 19.8065462.0252e−20 1.00000 B 0.840659 0.031369 CGxCW CEcHH 10.1 0.1 31.841.150449 2.8004e−20 1.00000 B 0.317610 0.001876 ACxNG CCcCC 22.7 1.746.9 16.272242 5.2201e−20 1.00000 B 0.484009 0.036780 CSxGI CCcCC 10.80.1 24.3 38.141746 6.0931e−20 1.00000 B 0.444444 0.003262 GSxKS CCcHH19.6 1.1 69.1 17.909474 5.1058e−19 1.00000 B 0.283647 0.015713 SGxSTCChHH 19.2 1.1 78.8 17.700094 9.4319e−19 1.00000 B 0.243655 0.013505SGxTT CChHH 19.7 1.2 60.8 17.285137 1.0837e−18 1.00000 B 0.3240130.019270 TWxIG EEcCC 12.3 0.4 12.3 19.628460 1.2719e−18 1.00000 B1.000000 0.030937 GTxKT CCcHH 22.0 1.7 105.1 15.901012 1.6887e−181.00000 B 0.209324 0.015815 YAxGR HHcCC 19.2 1.4 32.9 15.4600852.5350e−18 1.00000 B 0.583587 0.042130 LGxSI CCeEE 12.5 0.2 38.325.478322 3.4342e−18 1.00000 B 0.326371 0.006089 SPxSL ECcEE 42.9 12.8185.7  8.740430 4.1484e−18 1.00000 N 0.231018 0.068739 VGxTS CChHH 15.50.6 40.7 18.885040 1.3617e−17 1.00000 B 0.380835 0.015473 QFxTN CEcCC17.3 1.1 28.1 15.703799 1.4457e−17 1.00000 B 0.615658 0.039391 GTxVVCCcHH 4.0 0.1 2.0  6.359524 1.9940e−17 1.00000 B 2.000000 0.047121 SAxIGCCcCH 7.3 0.0 20.5 53.215652 3.5180e−17 1.00000 B 0.356098 0.000914GLxDW EEcCC 9.1 0.1 11.4 26.491413 1.0313e−16 1.00000 B 0.7982460.010192 QQxDY HChHH 1.0 0.1 1.0  4.123152 1.0485e−16 1.00000 B 1.0000000.055554 VVxGK CEeCC 1.0 0.1 1.0  4.267421 1.0524e−16 1.00000 B 1.0000000.052054 QSxGA HCcCC 1.0 0.0 1.0  4.675749 1.0617e−16 1.00000 B 1.0000000.043740 HExEN EEcCC 1.0 0.0 1.0  4.702523 1.0622e−16 1.00000 B 1.0000000.043264 FAxKL EEeCC 1.5 0.0 1.0  4.717887 1.0625e−16 1.00000 B 1.5000000.042995 ASxNT CEhHH 1.0 0.0 1.0  4.998624 1.0675e−16 1.00000 B 1.0000000.038482 DMxIT HCcCC 1.0 0.0 1.0  5.018322 1.0678e−16 1.00000 B 1.0000000.038192 YIxIH EEcCC 1.5 0.0 1.0  5.296248 1.0720e−16 1.00000 B 1.5000000.034423 TQxHG ECcCC 2.0 0.0 1.0  6.082239 1.0810e−16 1.00000 B 2.0000000.026320 GYxDN CCeEE 1.0 0.0 1.0 14.344343 1.1049e−16 1.00000 B 1.0000000.004837 QDxEG HHhHC 26.0 3.7 53.3 11.934122 1.7775e−16 1.00000 B0.487805 0.070194 DNxGK CCcCH 11.3 0.3 18.0 20.870892 2.9417e−16 1.00000B 0.627778 0.015727 SAxVG CCcCH 8.5 0.1 20.4 35.031051 3.2861e−161.00000 B 0.416667 0.002855 ASxRT HCcCC 17.7 1.4 31.9 14.2769885.1468e−16 1.00000 B 0.554859 0.042862 SSxKV HCeEE 42.6 13.8 198.0 8.026654 1.5452e−15 1.00000 N 0.215152 0.069800 GSxKT CCcHH 17.5 1.379.1 14.243727 8.9918e−15 1.00000 B 0.221239 0.016602 PTxNI CEeCC 14.30.4 10.3 16.216076 9.0764e−15 1.00000 B 1.388350 0.037693 GNxCR CCcCH6.5 0.0 14.5 46.467091 1.1355e−14 1.00000 B 0.448276 0.001343 PNxGKCCcCH 15.0 1.0 39.3 14.390978 1.3407e−14 1.00000 B 0.381679 0.024785GAxKT CCcHH 13.6 0.6 44.4 16.519183 1.4276e−14 1.00000 B 0.3063060.014092 KNxAC EEeCC 16.4 1.3 42.0 13.642975 2.3347e−14 1.00000 B0.390476 0.030201 QTxNR HChHH 17.2 1.5 46.4 12.932319 3.8897e−14 1.00000B 0.370690 0.032756 WGxGC ECcCC 20.7 2.2 129.6 12.427477 5.4394e−141.00000 B 0.159722 0.017317 NAxKT CCcHH 9.3 0.2 15.1 20.1473035.9572e−14 1.00000 B 0.615894 0.013678 CLxNI ECcCC 6.0 0.0 9.0 35.6160307.8888e−14 1.00000 B 0.666667 0.003134 AAxKT CCcHH 9.0 0.2 19.020.285697 8.6402e−14 1.00000 B 0.473684 0.010026 NTxVD CEeEE 32.3 9.8136.8  7.475662 1.3386e−13 1.00000 N 0.236111 0.071465 VGxSA CChHH 12.40.5 56.3 16.096540 1.7662e−13 1.00000 B 0.220249 0.009725 MExCT EEcCC8.0 0.1 11.1 20.524084 1.8190e−13 1.00000 B 0.720721 0.013363 RMxTFHHcCC 9.5 0.3 10.7 16.898890 2.0377e−13 1.00000 B 0.887850 0.028482QGxMS CChHH 7.0 0.1 7.0 21.093959 2.1381e−13 1.00000 B 1.000000 0.015488VAxKN ECcCC 20.9 2.9 46.7 10.827897 2.6347e−13 1.00000 B 0.4475370.062888 GGxGK CCcCH 18.1 1.8 107.1 12.168318 3.5653e−13 1.00000 B0.169001 0.017001 AGxGR CCcCH 8.9 0.2 33.4 21.578870 5.4421e−13 1.00000B 0.266467 0.004931 TNxRV CChHH 8.3 0.2 8.4 16.373784 1.1096e−12 1.00000B 0.988095 0.029661 NQxPN HHcHH 21.5 3.4 47.3 10.210149 1.1585e−121.00000 B 0.454545 0.071654 IVxYT ECcCC 9.3 0.3 23.0 17.5973981.8793e−12 1.00000 B 0.404348 0.011592 GHxAL CHhHC 9.9 0.4 12.914.873905 2.6141e−12 1.00000 B 0.767442 0.032551 TGxTF CChHH 8.0 0.2 9.816.341229 3.1327e−12 1.00000 B 0.816327 0.023619 SSxGN CCcCH 8.0 0.3 8.414.950912 3.5866e−12 1.00000 B 0.952381 0.032853 HNxVN HHhHH 6.0 0.1 7.023.122716 5.0946e−12 1.00000 B 0.857143 0.009497 DAxGK CCcCH 9.0 0.320.7 16.159672 5.1094e−12 1.00000 B 0.434783 0.014223 CGxCW CCcHH 6.60.1 35.8 27.620962 1.0933e−11 1.00000 B 0.184358 0.001570 GSxVE CEeEE15.9 2.0 34.1 10.186491 3.2680e−11 1.00000 B 0.466276 0.058124 TFxFYCCcEC 8.0 0.3 9.5 13.808045 3.3591e−11 1.00000 B 0.842105 0.033698 QGxGLCCcCH 8.0 0.3 12.9 15.079061 3.7782e−11 1.00000 B 0.620155 0.020813SAxIG CCcCC 11.3 0.7 34.2 12.776025 3.8879e−11 1.00000 B 0.3304090.020540 CSxGV CCcCC 7.8 0.2 26.0 18.754611 5.5937e−11 1.00000 B0.300000 0.006412 FMxIL CCcCC 8.8 0.3 17.0 14.990622 8.1728e−11 1.00000B 0.517647 0.019165 STxNT CCcHH 8.0 0.3 11.6 13.939347 8.2850e−111.00000 B 0.689655 0.026945 GQxIM CCcHH 5.0 0.0 6.0 24.219345 1.0267e−101.00000 B 0.833333 0.007033 YSxMS CCcEE 11.7 0.8 42.8 12.1638821.2625e−10 1.00000 B 0.273364 0.019069 TMxRI HHhHH 11.4 0.9 25.511.524995 1.5721e−10 1.00000 B 0.447059 0.033919 ACxGD CCcCC 9.1 0.485.9 14.278707 1.7497e−10 1.00000 B 0.105937 0.004366 QGxGK CCcCH 9.20.5 18.4 12.798647 2.1515e−10 1.00000 B 0.500000 0.025918 QCxSC CCcCH5.6 0.0 20.2 26.306118 3.4094e−10 1.00000 B 0.277228 0.002213 KRxNFCCcCE 7.3 0.2 20.3 15.996806 4.8000e−10 1.00000 B 0.359606 0.009803NGxGK CCcCH 11.0 0.8 49.0 11.320321 4.8018e−10 1.00000 B 0.2244900.016778 QVxGY CCcCH 7.8 0.3 7.1 12.079087 5.3401e−10 1.00000 B 1.0985920.046404 KExHP HHhCC 8.5 0.5 9.3 11.568737 5.4438e−10 1.00000 B 0.9139780.054304 RGxGR CChHH 8.0 0.5 10.0 11.451342 7.5878e−10 1.00000 B0.800000 0.045482 LTxWK ECcCC 6.2 0.1 10.0 16.936775 7.8155e−10 1.00000B 0.620000 0.013013 PGxGK CCcCH 19.1 3.3 118.9  8.743858 1.0050e−091.00000 B 0.160639 0.028106 APxVY CCeEE 9.2 0.5 111.5 12.5364201.6006e−09 1.00000 B 0.082511 0.004353 HHxEL EEeEC 4.4 0.0 10.431.598476 1.7714e−09 1.00000 B 0.423077 0.001852 NVxKS CCcHH 10.0 0.828.0 10.736324 1.8455e−09 1.00000 B 0.357143 0.027185 PExLT HHhHH 18.83.4 94.8  8.545879 2.0965e−09 1.00000 B 0.198312 0.035625 QGxCG CCcCC10.6 0.8 49.9 11.223443 2.0978e−09 1.00000 B 0.212425 0.015591 HKxQSHHhCC 5.3 0.1 7.1 19.188490 2.1092e−09 1.00000 B 0.746479 0.010555

TABLE 18 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityAGKxT CCHhH 45.2 1.2 109.0 40.761894 1.3250e−58 1.00000 B 0.4146790.010817 SGKxT CCHhH 44.9 1.2 149.1 39.478589 1.6432e−55 1.00000 B0.301140 0.008274 VGKxS CCHhH 30.5 0.4 78.0 49.113385 5.0372e−49 1.00000B 0.391026 0.004846 TKVxK EEEeE 92.3 24.5 367.4 14.170064 3.0926e−451.00000 N 0.251225 0.066733 STKxD CEEeE 64.9 15.7 230.1 12.8829891.5164e−37 1.00000 N 0.282051 0.068100 ACKxG CCCcC 34.1 2.0 46.423.183661 1.3729e−36 1.00000 B 0.734914 0.043173 GVGxS CCChH 36.4 2.9125.7 19.900725 3.7374e−29 1.00000 B 0.289578 0.023075 GFTxS CCHhH 25.71.3 42.2 21.824769 7.8086e−28 1.00000 B 0.609005 0.030577 CSAxI CCCcC13.3 0.1 22.7 43.660373 4.7467e−26 1.00000 B 0.585903 0.004048 KVDxKEEEeE 71.7 23.7 345.2 10.223365 2.3244e−24 1.00000 N 0.207706 0.068609QTGxT CCChH 19.0 0.8 22.9 20.352647 2.5890e−24 1.00000 B 0.8296940.036120 VACxN ECCcC 21.9 1.3 45.0 18.018290 2.2608e−21 1.00000 B0.486667 0.029818 SAGxG CCCcH 15.4 0.3 53.5 25.919968 3.9071e−21 1.00000B 0.287850 0.006351 TGTxK CCCcH 13.2 0.3 24.9 24.228491 2.1996e−191.00000 B 0.530120 0.011540 TQTxK CCCcH 15.3 0.6 14.3 17.4342832.3536e−19 1.00000 B 1.069930 0.044933 SGVxK CCCcH 18.3 0.9 60.918.724382 3.6394e−19 1.00000 B 0.300493 0.014423 GSGxS CCChH 19.9 1.377.0 16.792109 3.0892e−18 1.00000 B 0.258442 0.016279 GTGxT CCChH 26.92.9 127.9 14.224851 3.5090e−18 1.00000 B 0.210321 0.022755 GLTxW EECcC9.1 0.1 9.4 28.802900 3.8894e−18 1.00000 B 0.968085 0.010500 NVAxK EECcC24.2 2.7 48.5 13.323932 1.1195e−17 1.00000 B 0.498969 0.056658 NAGxTCCChH 9.3 0.1 14.9 32.073501 1.6197e−17 1.00000 B 0.624161 0.005573QDKxG HHHhC 27.2 3.9 57.3 12.295135 4.3110e−17 1.00000 B 0.4746950.067418 QSPxS EECcE 30.2 7.5 200.3  8.450279 7.0338e−17 1.00000 N0.150774 0.037434 QFNxN CECcC 17.1 1.2 28.1 14.748204 8.3663e−17 1.00000B 0.608541 0.043159 HTFxD ECCcC 1.0 0.1 1.0  4.054249 1.0466e−16 1.00000B 1.000000 0.057350 HIAxV EEEeC 3.0 0.1 1.0  4.139053 1.0490e−16 1.00000B 3.000000 0.055152 NKNxE EECcC 1.5 0.0 1.0  4.392794 1.0555e−16 1.00000B 1.500000 0.049269 KRSxA HHCcC 1.0 0.0 1.0  4.431513 1.0564e−16 1.00000B 1.000000 0.048454 FADxL EEEcC 1.5 0.0 1.0  4.615996 1.0605e−16 1.00000B 1.500000 0.044828 HESxN EECcC 1.0 0.0 1.0  4.763003 1.0634e−16 1.00000B 1.000000 0.042219 DASxN CCEhH 1.0 0.0 1.0  5.499204 1.0747e−16 1.00000B 1.000000 0.032009 EYFxE HHHcC 1.0 0.0 1.0  6.536892 1.0848e−16 1.00000B 1.000000 0.022867 SLFxE CCHhH 1.0 0.0 1.0  8.213495 1.0940e−16 1.00000B 1.000000 0.014607 GYRxN CCEeE 1.0 0.0 1.0 13.413602 1.1041e−16 1.00000B 1.000000 0.005527 DNAxK CCCcH 9.3 0.1 13.0 26.378846 2.7763e−161.00000 B 0.715385 0.009400 SSTxV HCEeE 44.7 14.5 217.1  8.2149383.2657e−16 1.00000 N 0.205896 0.066745 TGKxT CCHhH 13.0 0.4 60.819.353824 4.3808e−16 1.00000 B 0.213816 0.006992 YASxR HHCcC 17.3 1.331.5 14.260402 5.2564e−16 1.00000 B 0.549206 0.041639 VGKxA CCHhH 13.40.5 59.3 17.711339 4.4786e−15 1.00000 B 0.225970 0.008981 TKMxF CCCcC13.9 0.9 20.0 14.318899 1.3175e−14 1.00000 B 0.695000 0.043304 DGDxQCCCcC 26.3 4.4 66.8 10.811019 2.3355e−14 1.00000 B 0.393713 0.065788QTPxR HCHhH 17.2 1.5 46.4 12.981638 3.4999e−14 1.00000 B 0.3706900.032542 ASGxT HCCcC 19.7 2.2 49.7 12.173113 3.6080e−14 1.00000 B0.396378 0.043636 TGKxF CCHhH 8.0 0.1 11.3 22.053631 6.4552e−14 1.00000B 0.707965 0.011403 NTKxD CEEeE 32.3 9.6 139.1  7.572258 6.5452e−141.00000 N 0.232207 0.069229 KNVxC EEEcC 15.9 1.2 42.1 13.3253188.2636e−14 1.00000 B 0.377672 0.029601 SWGxG EECcC 20.9 2.4 146.211.989083 1.2563e−13 1.00000 B 0.142955 0.016530 LGNxC CCCcC 8.0 0.114.5 22.390499 1.2699e−13 1.00000 B 0.551724 0.008606 GNIxR CCCcH 5.00.0 10.7 52.390153 1.7043e−13 1.00000 B 0.467290 0.000849 PGHxA CCHhH11.3 0.5 18.8 15.376713 2.0088e−13 1.00000 B 0.601064 0.026934 PPGxPCCCcC 24.9 4.1 88.4 10.603352 2.3088e−13 1.00000 B 0.281674 0.045833PTVVxI CEEcC 12.3 0.4 9.3 15.254719 2.7816e−13 1.00000 B 1.3225810.038429 AGVxR CCChH 7.8 0.1 21.6 26.565655 4.0849e−13 1.00000 B0.361111 0.003920 GYWxD CCCeE 6.6 0.1 6.1 26.353923 4.9686e−13 1.00000 B1.081967 0.008706 LGFxI CCEeE 9.2 0.2 34.0 19.338446 6.4511e−13 1.00000B 0.270588 0.006387 AAGxT CCChH 9.0 0.2 21.1 18.175548 7.2886e−131.00000 B 0.426540 0.011145 VGKxT CCHhH 12.0 0.6 68.6 14.8069529.9951e−13 1.00000 B 0.174927 0.008720 GAGxT CCChH 13.6 0.9 51.813.538893 1.7051e−12 1.00000 B 0.262548 0.017297 GSTxE CEEeE 15.9 1.828.0 10.991903 2.4901e−12 1.00000 B 0.567857 0.063033 TFKxY CCCeC 9.50.5 9.5 12.661819 9.1849e−12 1.00000 B 1.000000 0.055941 CLGxI ECCcC 6.00.1 10.0 23.464775 1.4656e−11 1.00000 B 0.600000 0.006440 DAAxK CCCcH9.0 0.3 22.0 15.053553 1.8970e−11 1.00000 B 0.409091 0.015289 GSGxTCCChH 18.5 2.5 88.2 10.388049 2.1546e−11 1.00000 B 0.209751 0.027825LGIxI CCEeE 8.5 0.2 25.4 17.263867 2.6410e−11 1.00000 B 0.3346460.009114 QGSxK CCCcH 7.2 0.1 14.1 18.907162 2.7340e−11 1.00000 B0.510638 0.009986 IVNxT ECCcC 9.3 0.4 25.5 15.158694 2.7348e−11 1.00000B 0.364706 0.013852 FMRxL CCCcC 8.8 0.3 16.8 16.058362 2.8289e−111.00000 B 0.523810 0.017022 DKPxY CCCcC 13.2 1.3 21.2 10.5941093.0412e−11 1.00000 B 0.622642 0.063119 CSAxV CCCcC 7.8 0.2 23.019.273690 3.4354e−11 1.00000 B 0.339130 0.006882 QGKxS CCHhH 7.7 0.2 7.515.542889 3.4721e−11 1.00000 B 1.026667 0.030111 FPExL HHHhH 17.3 2.371.5 10.172199 5.1552e−11 1.00000 B 0.241958 0.031580 VSWxR EEEcC 4.30.0 5.3 43.831075 5.4189e−11 1.00000 B 0.811321 0.001811 ETGxS ECCcC17.6 2.4 62.0 10.000804 6.3892e−11 1.00000 B 0.283871 0.038748 NGGxMECCcH 8.1 0.3 11.2 14.070255 6.7783e−11 1.00000 B 0.723214 0.028125DMNxE CCChH 9.7 0.6 12.1 12.416785 7.4545e−11 1.00000 B 0.8016530.046907 NVGxS CCChH 10.0 0.6 26.6 12.303756 1.6309e−10 1.00000 B0.375940 0.022460 YTPxL CCCcC 11.1 0.8 39.8 11.762389 2.0298e−10 1.00000B 0.278894 0.019713 TGAxK CCCcH 8.1 0.3 16.4 14.066473 2.2656e−101.00000 B 0.493902 0.019052 GTFxC CCCcC 7.0 0.3 8.3 13.618683 3.1057e−101.00000 B 0.843373 0.030500 HALxV EEEeE 5.0 0.0 20.1 25.7410173.3997e−10 1.00000 B 0.248756 0.001853 AGIxR CCChH 5.9 0.1 21.224.217537 3.4816e−10 1.00000 B 0.278302 0.002752 GAGxS CCChH 11.0 0.848.0 11.250818 5.2604e−10 1.00000 B 0.229167 0.017318 ELCxL ECCcC 7.00.3 9.1 13.542555 5.3172e−10 1.00000 B 0.769231 0.028045 DHGxT CCChH 7.00.2 29.3 15.970830 5.6202e−10 1.00000 B 0.238908 0.006257 VGKxC CCHhH10.0 0.6 60.7 12.076594 5.7001e−10 1.00000 B 0.164745 0.010060 NQTxNHHChH 17.4 2.9 46.3  8.876430 6.1701e−10 1.00000 B 0.375810 0.061769GGTxK CCCcH 8.0 0.3 32.5 13.907304 6.5278e−10 1.00000 B 0.2461540.009501 GLGxS ECCeE 5.5 0.1 6.7 20.909266 8.0589e−10 1.00000 B 0.8208960.010176 WGRxV HHHhH 7.3 0.2 26.2 15.359753 1.0620e−09 1.00000 B0.278626 0.008189 AGIxR CCCcH 7.5 0.2 24.2 14.824604 1.6308e−09 1.00000B 0.309917 0.010005 QCGxC CCCcH 7.1 0.2 20.2 14.323869 1.7811e−091.00000 B 0.351485 0.011512 SSTxN CCCcH 7.0 0.3 9.0 12.195858 2.0164e−091.00000 B 0.777778 0.034617 MELxT EECcC 10.0 0.8 29.5 10.7062362.0986e−09 1.00000 B 0.338983 0.025898 QGIxS CCHhH 7.0 0.3 11.212.503979 3.1879e−09 1.00000 B 0.625000 0.026366 HGKxT CCHhH 7.0 0.238.9 14.055817 3.5464e−09 1.00000 B 0.179949 0.005994 ATNxR CCChH 9.30.4 7.4 10.764547 4.1930e−09 1.00000 B 1.256757 0.060028 GQGxG CCChH 8.00.5 14.1 11.032259 4.9378e−09 1.00000 B 0.567376 0.034108 RIVxY EECcC10.8 1.0 25.1  9.968876 5.1361e−09 1.00000 B 0.430279 0.040063 RGLxRCCHhH 7.0 0.3 10.7 11.925372 5.1481e−09 1.00000 B 0.654206 0.030208

TABLE 19 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityAGKTT CCHHH 30.3 0.2 53.3 60.465312 5.5259e−56 1.00000 B 0.5684800.004656 TKVDK EEEEE 86.3 20.3 363.4 15.071953 6.9306e−51 1.00000 N0.237479 0.055879 STKVD CEEEE 61.6 13.0 230.1 13.904790 2.1619e−431.00000 N 0.267710 0.056344 GVGKS CCCHH 34.9 1.2 109.6 31.3864291.1635e−40 1.00000 B 0.318431 0.010653 KVDKK EEEEE 71.2 19.4 341.612.131059 1.4989e−33 1.00000 N 0.208431 0.056672 CSAGI CCCCC 10.8 0.021.7 119.020953 6.6042e−30 1.00000 B 0.497696 0.000379 SGKST CCHHH 19.20.4 74.8 29.140926 2.5218e−26 1.00000 B 0.256684 0.005585 GFTNS CCHHH24.7 1.3 41.2 20.894474 2.9243e−26 1.00000 B 0.599515 0.031442 VGKSSCCHHH 15.0 0.2 36.0 36.980645 3.1208e−26 1.00000 B 0.416667 0.004492SGKTT CCHHH 19.7 0.5 60.8 27.874101 6.8319e−26 1.00000 B 0.3240130.007883 GSGKS CCCHH 19.6 0.6 66.7 25.190609 3.6713e−24 1.00000 B0.293853 0.008626 SGVGK CCCCH 18.3 0.5 53.4 25.703105 6.9392e−24 1.00000B 0.342697 0.009079 NVACK EECCC 24.2 1.6 45.0 18.282352 1.9905e−231.00000 B 0.537778 0.035242 VGKTS CCHHH 15.5 0.3 39.7 29.8026923.1710e−23 1.00000 B 0.390428 0.006628 DNAGK CCCCH 9.3 0.0 13.051.914426 1.6236e−21 1.00000 B 0.715385 0.002458 NAGKT CCCHH 9.3 0.013.9 52.186777 2.0505e−21 1.00000 B 0.669065 0.002274 GTGKT CCCHH 22.01.3 99.0 18.387859 6.8722e−21 1.00000 B 0.222222 0.012987 SSTKV HCEEE41.4 11.0 198.1 9.427547 9.0951e−21 1.00000 N 0.208985 0.055556 QTGKTCCCHH 15.3 0.6 18.2 20.141893 1.2540e−20 1.00000 B 0.840659 0.030377TQTGK CCCCH 15.3 0.6 14.3 18.234366 7.0811e−20 1.00000 B 1.0699300.041235 AGIGR CCCCH 7.5 0.0 16.7 77.399169 1.4536e−19 1.00000 B0.449102 0.000561 VACKN ECCCC 20.9 1.5 43.0 16.412549 2.2938e−19 1.00000B 0.486047 0.033792 ACKNG CCCCC 21.6 1.7 43.0 15.804325 3.8946e−191.00000 B 0.502326 0.038517 NTKVD CEEEE 32.3 7.8 136.3 9.0015055.8508e−19 1.00000 N 0.236977 0.057495 VGKSA CCHHH 12.4 0.2 44.027.218777 9.6246e−19 1.00000 B 0.281818 0.004586 TGTGK CCCCH 13.2 0.323.9 22.531929 1.1028e−18 1.00000 B 0.552301 0.013841 CSAGV CCCCC 6.80.0 21.0 90.676937 3.9652e−18 1.00000 B 0.323810 0.000267 GLTDW EECCC9.1 0.1 9.4 28.126064 5.9368e−18 1.00000 B 0.968085 0.011006 YASGR HHCCC17.3 1.1 30.0 16.136826 9.8425e−18 1.00000 B 0.576667 0.035026 TDVVGCCHHH 2.0 0.0 2.0 9.169227 1.0079e−17 1.00000 B 1.000000 0.023236 GTDVVCCCHH 4.0 0.1 2.0 6.652325 1.8372e−17 1.00000 B 2.000000 0.043240 ASGRTHCCCC 17.7 1.1 31.9 15.804729 2.5121e−17 1.00000 B 0.554859 0.035695AAGKT CCCHH 9.0 0.1 19.0 32.243836 2.5944e−17 1.00000 B 0.4736840.004047 GAGKT CCCHH 13.6 0.4 44.3 21.167039 3.8339e−17 1.00000 B0.306998 0.008867 QSTYS CCCEE 1.3 0.1 1.0 4.271212 1.0525e−16 1.00000 B1.300000 0.051966 IASVA EEECC 3.0 0.1 1.0 4.319109 1.0537e−16 1.00000 B3.000000 0.050878 HTFID ECCCC 1.0 0.0 1.0 4.414173 1.0560e−16 1.00000 B1.000000 0.048816 HIASV EEEEC 3.0 0.0 1.0 4.435998 1.0565e−16 1.00000 B3.000000 0.048360 SRTGT CCCCC 1.0 0.0 1.0 4.483287 1.0576e−16 1.00000 B1.000000 0.047394 PSLPT CCCCC 1.0 0.0 1.0 4.729112 1.0627e−16 1.00000 B1.000000 0.042800 FADKL EEECC 1.5 0.0 1.0 4.930669 1.0664e−16 1.00000 B1.500000 0.039508 HESEN EECCC 1.0 0.0 1.0 4.970215 1.0670e−16 1.00000 B1.000000 0.038906 GTMKP CCCCC 1.7 0.0 1.0 5.689319 1.0770e−16 1.00000 B1.700000 0.029969 TQQHG ECCCC 2.0 0.0 1.0 6.095078 1.0811e−16 1.00000 B2.000000 0.026212 YIKIH EECCC 1.5 0.0 1.0 6.298304 1.0829e−16 1.00000 B1.500000 0.024589 ITTLD EEEEE 1.0 0.0 1.0 6.443160 1.0841e−16 1.00000 B1.000000 0.023521 NALAS CCCCC 1.0 0.0 1.0 7.078294 1.0885e−16 1.00000 B1.000000 0.019569 RGFSG CCECC 1.0 0.0 1.0 7.563653 1.0911e−16 1.00000 B1.000000 0.017180 SLFLE CCHHH 1.0 0.0 1.0 8.389016 1.0947e−16 1.00000 B1.000000 0.014010 GYRDN CCEEE 1.0 0.0 1.0 12.986148 1.1037e−16 1.00000 B1.000000 0.005895 QFNTN CECCC 16.8 1.1 28.1 15.369429 1.1857e−16 1.00000B 0.597865 0.038692 DAAGK CCCCH 9.0 0.1 20.1 29.526979 1.4194e−161.00000 B 0.447761 0.004549 LGNIC CCCCC 6.0 0.0 9.0 57.956075 2.3546e−161.00000 B 0.666667 0.001188 CLGNI ECCCC 6.0 0.0 9.0 55.536718 3.9218e−161.00000 B 0.666667 0.001294 PPGPP CCCCC 16.8 1.2 31.0 14.5171161.0146e−15 1.00000 B 0.541935 0.038746 GNICR CCCCH 5.0 0.0 10.786.957797 1.0862e−15 1.00000 B 0.467290 0.000309 QDKEG HHHHC 23.5 3.053.3 12.128908 1.5706e−15 1.00000 B 0.440901 0.056696 AGVGR CCCHH 7.30.0 20.1 39.450567 2.1921e−15 1.00000 B 0.363184 0.001691 HALAV EEEEE5.0 0.0 7.7 68.668141 6.5384e−15 1.00000 B 0.649351 0.000688 NVGKS CCCHH10.0 0.2 23.0 20.863516 7.0957e−15 1.00000 B 0.434783 0.009643 SAGIGCCCCH 5.9 0.0 20.5 70.678886 8.0219e−15 1.00000 B 0.287805 0.000339TGKTF CCHHH 8.0 0.1 9.8 23.661871 9.8853e−15 1.00000 B 0.816327 0.011470GSGKT CCCHH 16.5 1.1 77.1 14.568931 1.4235e−14 1.00000 B 0.2140080.014651 QTPNR HCHHH 17.2 1.5 46.4 13.229385 2.0671e−14 1.00000 B0.370690 0.031495 SAGVG CCCCH 7.5 0.0 20.4 33.668542 2.0857e−14 1.00000B 0.367647 0.002407 GSTVE CEEEE 15.9 1.4 24.4 12.865137 2.1829e−141.00000 B 0.651639 0.055473 AGIGR CCCHH 5.9 0.0 20.2 61.0609943.4266e−14 1.00000 B 0.292079 0.000461 MELCT EECCC 8.0 0.1 11.121.886741 6.6835e−14 1.00000 B 0.720721 0.011785 KNVAC EEECC 15.9 1.242.1 13.367493 7.6225e−14 1.00000 B 0.377672 0.029438 ACNGD CCCCC 5.00.0 6.0 48.691508 9.9218e−14 1.00000 B 0.833333 0.001753 RGLGR CCHHH 7.00.1 7.0 21.735542 1.4144e−13 1.00000 B 1.000000 0.014601 TWNIG EECCC12.3 0.3 9.3 15.690258 1.7089e−13 1.00000 B 1.322581 0.036401 PTWNICEECC 12.3 0.3 9.3 15.586625 1.9168e−13 1.00000 B 1.322581 0.036869GGTGK CCCCH 8.0 0.1 32.0 22.161607 5.8435e−13 1.00000 B 0.2500000.003960 VGKSN CCHHH 6.3 0.0 11.0 31.650387 6.5990e−13 1.00000 B0.572727 0.003570 GAGKS CCCHH 9.0 0.2 22.4 18.251205 7.6963e−13 1.00000B 0.401786 0.010409 TGAGK CCCCH 8.1 0.2 15.0 19.304260 1.5160e−121.00000 B 0.540000 0.011377 QGIMS CCHHH 5.0 0.0 5.0 33.817618 1.5630e−121.00000 B 1.000000 0.004353 DHGKT CCCHH 7.0 0.1 29.2 24.3006802.0219e−12 1.00000 B 0.239726 0.002784 IVNYT ECCCC 9.3 0.3 22.017.173156 2.6007e−12 1.00000 B 0.422727 0.012703 TGKTT CCHHH 10.0 0.449.2 15.782827 4.3075e−12 1.00000 B 0.203252 0.007617 FMRIL CCCCC 8.80.2 15.0 17.816749 4.4112e−12 1.00000 B 0.586667 0.015652 VGKST CCHHH9.7 0.3 41.3 17.282948 5.1363e−12 1.00000 B 0.234867 0.007218 PNVGKCCCCH 8.5 0.2 24.0 17.650727 1.7561e−11 1.00000 B 0.354167 0.009250TFKFY CCCEC 8.0 0.3 9.5 14.144154 2.3311e−11 1.00000 B 0.842105 0.032186SAGIG CCCCC 7.8 0.2 18.3 19.277002 2.5815e−11 1.00000 B 0.4262300.008662 SPSSL ECCEE 22.6 6.2 113.2 6.737919 3.2449e−11 1.00000 N0.199647 0.055120 AGKST CCHHH 8.6 0.3 24.6 16.358492 5.5030e−11 1.00000B 0.349593 0.010673 NQTPN HHCHH 17.4 2.5 46.3 9.807330 5.7989e−111.00000 B 0.375810 0.052976 AGKTS CCHHH 4.6 0.0 6.5 45.221979 5.9445e−111.00000 B 0.707692 0.001587 QGSGK CCCCH 7.2 0.2 12.9 17.2665877.6089e−11 1.00000 B 0.558140 0.013027 STGNT CCCHH 8.0 0.3 11.613.943602 8.2471e−11 1.00000 B 0.689655 0.026930 HGKTT CCHHH 7.0 0.135.2 18.613204 8.4185e−11 1.00000 B 0.198864 0.003878 SGSGK CCCCH 6.70.1 22.8 22.484912 8.4213e−11 1.00000 B 0.293860 0.003809 GQGIM CCCHH5.0 0.0 5.0 22.627078 8.4618e−11 1.00000 B 1.000000 0.009671 YSTMS CCCEE11.7 0.8 42.8 12.014476 1.5892e−10 1.00000 B 0.273364 0.019490 QTGTGCCCCC 7.5 0.2 10.0 15.134947 2.3135e−10 1.00000 B 0.750000 0.023592VSWGR EEECC 4.3 0.0 5.3 36.339637 2.4138e−10 1.00000 B 0.811321 0.002632FTVAQ CCHHH 7.1 0.2 15.0 16.089718 2.4804e−10 1.00000 B 0.4733330.012462

TABLE 20 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityLxxxxR CchhhH 243.0 57.8 1351.9 24.885394  2.8521e−136 1.00000 N0.179747 0.042782 GxxxxQ CcchhH 255.1 81.2 1223.1 19.980536 1.2830e−881.00000 N 0.208568 0.066361 LxxxxQ CchhhH 126.4 29.8 922.6 18.0071724.5848e−72 1.00000 N 0.137004 0.032258 LxxxxK CchhhH 149.3 41.7 947.417.047502 7.0481e−65 1.00000 N 0.157589 0.043999 GxxxxE CcchhH 400.5186.8 2725.7 16.199779 4.6835e−59 1.00000 N 0.146935 0.068536 LxxxxMCchhhH 61.6 11.4 519.7 15.057313 1.4748e−50 1.00000 N 0.118530 0.021888GxxxxT CcchhH 210.7 80.5 1540.2 14.898100 3.9858e−50 1.00000 N 0.1368000.052292 LxxxxI CchhhH 120.9 37.9 1893.1 13.610400 5.3167e−42 1.00000 N0.063864 0.020034 AxxxxV HhhhcC 87.4 23.0 1099.8 13.589463 9.7121e−421.00000 N 0.079469 0.020879 ExxxxW CcchhH 36.1 5.3 134.0 13.6779581.4188e−41 1.00000 N 0.269403 0.039434 IxxxxR CchhhH 79.2 20.1 469.113.463888 5.9268e−41 1.00000 N 0.168834 0.042888 SxxxxR CchhhH 124.841.7 647.7 13.306610 3.0825e−40 1.00000 N 0.192682 0.064369 AxxxxRCchhhH 115.3 37.0 706.6 13.228266 9.2344e−40 1.00000 N 0.163176 0.052343AxxxxI HhhhcC 71.2 17.1 836.7 13.234870 1.3942e−39 1.00000 N 0.0850960.020406 ExxxxR EecceE 59.1 13.4 159.8 13.057590 1.8573e−38 1.00000 N0.369837 0.083731 RxxxxE HhhccC 173.9 70.9 874.0 12.761204 2.9847e−371.00000 N 0.198970 0.081120 SxxxxQ CchhhH 107.1 34.6 557.3 12.7346765.8204e−37 1.00000 N 0.192177 0.062044 NxxxxE CcchhH 188.1 80.7 1090.712.430866 1.8292e−35 1.00000 N 0.172458 0.073955 GxxxxS CcchhH 154.160.6 1208.3 12.329694 7.0867e−35 1.00000 N 0.127535 0.050132 LxxxxLCchhhH 154.3 60.1 2989.1 12.264411 1.5679e−34 1.00000 N 0.0516210.020122 TxxxxR CchhhH 97.2 31.2 509.4 12.189503 5.4680e−34 1.00000 N0.190813 0.061279 SxxxxR ChhhhH 261.0 129.5 1853.7 11.982428 3.8015e−331.00000 N 0.140799 0.069857 FxxxxR CchhhH 53.8 12.6 341.3 11.8078829.6778e−32 1.00000 N 0.157633 0.036994 SxxxxE CcchhH 192.1 88.4 1305.411.424853 2.9571e−30 1.00000 N 0.147158 0.067710 VxxxxF CcchhH 39.3 7.9319.7 11.295066 5.2957e−29 1.00000 N 0.122928 0.024762 FxxxxE EcchhH34.0 6.3 182.6 11.217448 1.6197e−28 1.00000 N 0.186199 0.034562 GxxxxDCcchhH 262.4 137.5 2156.0 11.007428 2.8665e−28 1.00000 N 0.1217070.063779 TxxxxT EecceE 82.4 27.3 361.9 10.952964 9.5962e−28 1.00000 N0.227687 0.075539 TxxxxE CcchhH 153.7 67.3 1094.5 10.868932 1.6117e−271.00000 N 0.140429 0.061501 KxxxxW EecceE 36.7 7.5 127.6 10.9663822.1756e−27 1.00000 N 0.287618 0.058953 DxxxxR CchhhH 136.7 58.0 811.510.718357 8.6960e−27 1.00000 N 0.168453 0.071505 YxxxxE CcchhH 85.7 29.3538.1 10.711761 1.2450e−26 1.00000 N 0.159264 0.054469 LxxxxI HhhccC81.5 26.8 1641.0 10.661368 2.1892e−26 1.00000 N 0.049665 0.016319 RxxxxFEeeccC 48.1 12.1 197.8 10.669917 3.4327e−26 1.00000 N 0.243175 0.061253KxxxxY EecceE 31.7 6.0 126.7 10.691459 5.1661e−26 1.00000 N 0.2501970.047719 GxxxxR CchhhH 118.7 48.8 850.2 10.297931 7.7223e−25 1.00000 N0.139614 0.057438 GxxxxR CcchhH 133.1 57.9 856.2 10.244740 1.2603e−241.00000 N 0.155454 0.067572 ExxxxE CcchhH 191.6 95.5 1299.3 10.2131541.4953e−24 1.00000 N 0.147464 0.073517 GxxxxN CcchhH 104.6 41.2 673.710.207393 2.0976e−24 1.00000 N 0.155262 0.061083 QxxxxT EecceE 35.6 7.8134.6 10.298441 2.4065e−24 1.00000 N 0.264487 0.057628 VxxxxQ EchhhC23.8 1.4 40.9 19.211871 4.9634e−24 1.00000 B 0.581907 0.034401 RxxxxDHhhccC 174.6 85.9 1073.5  9.970399 1.8063e−23 1.00000 N 0.1626460.080061 FxxxxE CcchhH 87.8 32.5 685.4  9.926259 3.9216e−23 1.00000 N0.128100 0.047474 LxxxxV CchhhH 90.3 33.8 1719.7  9.813784 1.1574e−221.00000 N 0.052509 0.019657 RxxxxH HhhccC 65.2 21.7 297.8  9.7034374.3224e−22 1.00000 N 0.218939 0.072826 GxxxxY CcchhH 68.3 23.1 533.9 9.630341 8.3399e−22 1.00000 N 0.127927 0.043196 AxxxxE CcchhH 148.070.1 1242.5  9.573740 9.3271e−22 1.00000 N 0.119115 0.056438 WxxxxRCchhhH 33.4 7.5 151.7  9.659593 1.3620e−21 1.00000 N 0.220171 0.049712DxxxxT EccccE 70.6 24.4 581.0  9.569481 1.4539e−21 1.00000 N 0.1215150.041937 PxxxxQ CcchhH 109.4 46.5 1083.7  9.421620 4.5216e−21 1.00000 N0.100950 0.042935 DxxxxR ChhhhH 237.0 133.2 1783.5  9.344319 7.0694e−211.00000 N 0.132885 0.074710 GxxxxK CcchhH 153.6 75.4 1023.0  9.3489507.7771e−21 1.00000 N 0.150147 0.073750 TxxxxR ChhhhH 192.4 101.8 1444.8 9.314664 9.9140e−21 1.00000 N 0.133167 0.070455 RxxxxQ CcchhH 80.6 30.6502.4  9.316053 1.4468e−20 1.00000 N 0.160430 0.060976 YxxxxG EecccC128.5 59.1 1454.7  9.226183 2.6007e−20 1.00000 N 0.088334 0.040595QxxxxE CcchhH 111.8 49.3 708.3  9.233590 2.6009e−20 1.00000 N 0.1578430.069571 DxxxxE CcchhH 154.5 77.4 1117.3  9.079327 9.3679e−20 1.00000 N0.138280 0.069298 FxxxxY CchhhC 30.2 6.8 172.7  9.178860 1.3184e−191.00000 N 0.174870 0.039245 ExxxxS HhhccC 134.5 64.7 919.1  8.9996182.0332e−19 1.00000 N 0.146339 0.070398 NxxxxR CchhhH 74.6 28.5 442.8 8.941105 4.6087e−19 1.00000 N 0.168473 0.064272 QxxxxL EecceE 42.9 12.1459.9  8.967760 5.6147e−19 1.00000 N 0.093281 0.026328 ExxxxV EcceeE46.8 14.0 318.4  8.939876 6.6359e−19 1.00000 N 0.146985 0.044109 VxxxxREchhhC 25.4 2.5 69.9 14.588668 8.5240e−19 1.00000 B 0.363376 0.036434ExxxxK HchhhH 29.4 6.9 82.3  8.942929 1.1236e−18 1.00000 N 0.3572300.083914 DxxxxQ ChhhhH 152.3 77.8 1117.8  8.751110 1.7751e−18 1.00000 N0.136250 0.069630 KxxxxY HhhccC 67.0 24.7 384.0  8.786447 1.9357e−181.00000 N 0.174479 0.064410 ExxxxL EecceE 40.3 11.3 277.3  8.8269982.0686e−18 1.00000 N 0.145330 0.040651 CxxxxY EecccC 27.4 3.0 127.414.220807 2.5238e−18 1.00000 B 0.215071 0.023644 PxxxxR CchhhH 112.251.7 866.2  8.685640 3.5307e−18 1.00000 N 0.129531 0.059641 GxxxxQCchhhH 65.4 23.9 462.5  8.714553 3.6676e−18 1.00000 N 0.141405 0.051690GxxxxQ CcehhH 28.4 6.7 87.1  8.747114 6.3844e−18 1.00000 N 0.3260620.076678 NxxxxK CchhhH 81.3 33.5 456.0  8.591494 9.3418e−18 1.00000 N0.178289 0.073378 YxxxxH CccccE 25.8 5.6 128.0  8.709907 9.9702e−181.00000 N 0.201563 0.043878 ExxxxK EcceeE 43.1 13.1 168.8  8.6063011.3067e−17 1.00000 N 0.255332 0.077849 LxxxxE CcchhH 116.0 54.7 1020.9 8.516601 1.4929e−17 1.00000 N 0.113625 0.053595 ExxxxR CchhhH 96.4 42.8631.6  8.492481 1.9932e−17 1.00000 N 0.152628 0.067721 ExxxxR EcceeE39.2 11.5 139.1  8.542044 2.4730e−17 1.00000 N 0.281812 0.082523 IxxxxLCchhhH 79.6 32.1 1654.6  8.474998 2.5182e−17 1.00000 N 0.048108 0.019383SxxxxQ CcchhH 97.8 43.8 663.1  8.432856 3.2796e−17 1.00000 N 0.1474890.066115 KxxxxN HhhccC 132.1 66.5 806.8  8.389233 4.2077e−17 1.00000 N0.163733 0.082483 ExxxxR HhhccC 116.1 55.9 742.2  8.375368 4.9567e−171.00000 N 0.156427 0.075303 HxxxxR CchhhH 42.2 12.9 198.2  8.4412545.3279e−17 1.00000 N 0.212916 0.065049 MxxxxR CchhhH 51.3 17.3 353.0 8.401305 6.2683e−17 1.00000 N 0.145326 0.048896 WxxxxK HhhhcC 38.8 11.2266.7  8.429782 6.3105e−17 1.00000 N 0.145482 0.041973 GxxxxF EecceE33.3 8.7 334.0  8.436510 6.9899e−17 1.00000 N 0.099701 0.026101 VxxxxRCchhhH 75.7 30.6 650.5  8.356763 7.0348e−17 1.00000 N 0.116372 0.047016VxxxxF CchhhH 40.9 12.1 688.2  8.383240 8.7602e−17 1.00000 N 0.0594300.017513 RxxxxR HhhhhH 509.6 359.0 4907.4  8.254956 9.5544e−17 1.00000 N0.103843 0.073158 SxxxxQ ChhhhH 176.9 97.8 1537.4  8.267115 1.0620e−161.00000 N 0.115064 0.063607 VxxxxE EcchhH 59.9 21.9 499.1  8.2981751.3176e−16 1.00000 N 0.120016 0.043910 GxxxxA CcchhH 152.0 80.0 1799.4 8.235044 1.4447e−16 1.00000 N 0.084473 0.044459 RxxxxE EecceE 36.6 10.6131.4  8.302230 1.9387e−16 1.00000 N 0.278539 0.080969 IxxxxY EcceeE25.5 5.7 229.8  8.350186 1.9949e−16 1.00000 N 0.110966 0.024988 YxxxxQEccccC 41.7 12.9 277.2  8.238435 2.8485e−16 1.00000 N 0.150433 0.046375KxxxxE CcchhH 180.8 102.1 1300.8  8.119417 3.5770e−16 1.00000 N 0.1389910.078458 RxxxxL HhhccC 95.2 43.3 774.6  8.128103 4.1443e−16 1.00000 N0.122902 0.055843 ExxxxY EcceeE 29.7 7.7 170.1  8.125602 1.0025e−151.00000 N 0.174603 0.045189 ExxxxD HhhheC 18.8 1.6 44.9 13.9806281.0075e−15 1.00000 B 0.418708 0.035042 QxxxxQ CchhhH 45.1 15.0 238.9 8.045709 1.2643e−15 1.00000 N 0.188782 0.062644

TABLE 21 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityVxxxNF CcchHH 23.5 0.1 36.1 60.676785 1.6831e−46 1.00000 B 0.6509700.004120 TxxxKT CcccHH 42.4 3.9 131.3 19.889388 9.5748e−32 1.00000 B0.322925 0.029453 AxxxGV HhhhCC 45.2 9.8 582.5 11.387117 1.5163e−291.00000 N 0.077597 0.016857 ExxxMD HhhhEC 16.7 0.2 36.2 35.3931816.7544e−27 1.00000 B 0.461326 0.006027 GxxxST CcchHH 41.3 9.3 215.210.727154 2.2945e−26 1.00000 N 0.191914 0.043218 GxxxTT CcchHH 45.0 10.8228.6 10.664870 3.9274e−26 1.00000 N 0.196850 0.047226 LxxxGK CcccCH29.0 1.9 120.0 20.108167 4.1285e−26 1.00000 B 0.241667 0.015428 SxxxDKCeeeEE 60.1 17.8 256.6 10.374931 5.7844e−25 1.00000 N 0.234217 0.069505PxxxIG CeecCC 14.3 0.2 13.4 29.692131 3.6368e−24 1.00000 B 1.0671640.014972 SxxxKS CcccHH 28.0 5.2 140.5 10.214096 8.4052e−24 1.00000 N0.199288 0.036881 LxxxVM CchhHH 23.7 1.4 59.7 19.223495 6.7876e−231.00000 B 0.396985 0.023116 VxxxNG EcccCC 29.1 5.8 121.9  9.9709608.5736e−23 1.00000 N 0.238720 0.047201 DxxxGK CcccCH 35.1 4.2 204.515.193499 9.8658e−22 1.00000 B 0.171638 0.020627 YxxxNE HhhhHH 27.3 5.5107.9  9.499449 8.3765e−21 1.00000 N 0.253012 0.051287 DxxxKT CcccHH24.5 2.0 64.1 15.998384 4.4565e−20 1.00000 B 0.382215 0.031767 QxxxLGCcccHH 18.4 0.9 36.3 18.490167 7.6666e−20 1.00000 B 0.506887 0.025267QxxxWY HhhhHC 11.5 0.3 11.1 20.996615 2.3636e−18 1.00000 B 1.0360360.024560 YxxxFQ CcccCC 18.6 1.1 41.8 16.836828 3.0671e−18 1.00000 B0.444976 0.026523 AxxxGI HhhhCC 29.9 6.9 432.7  8.779901 4.3999e−181.00000 N 0.069101 0.016053 CxxxIC EcccCC 7.0 0.0 12.0 50.2275352.2267e−17 1.00000 B 0.583333 0.001612 TxxxKK EeeeEE 69.9 27.5 416.3 8.363251 7.0078e−17 1.00000 N 0.167908 0.066081 MxxxDA HhccCH 1.0 0.01.0  5.293417 1.0720e−16 1.00000 B 1.000000 0.034459 QxxxSL EeccEE 27.96.7 256.2  8.321559 2.2276e−16 1.00000 N 0.108899 0.026065 LxxxYH HhhhHH29.3 4.2 149.9 12.332883 2.6305e−16 1.00000 B 0.195464 0.028332 RxxxPEHhhcCC 28.5 7.2 111.5  8.193404 6.1741e−16 1.00000 N 0.255605 0.064712QxxxGS CcccEC 11.5 0.3 38.4 20.426447 4.2192e−15 1.00000 B 0.2994790.007887 WxxxFT HhhcCC 9.4 0.2 17.9 23.668916 6.5801e−15 1.00000 B0.525140 0.008599 SxxxGR CcccHH 15.8 1.0 67.1 15.237596 9.2692e−151.00000 B 0.235469 0.014337 NxxxGK CcccCH 16.9 1.3 53.7 14.0615901.1001e−14 1.00000 B 0.314711 0.023575 NxxxQF CcccCE 17.8 1.5 51.113.545332 1.1983e−14 1.00000 B 0.348337 0.029216 YxxxRT HhccCC 18.3 1.947.4 12.329519 5.9076e−14 1.00000 B 0.386076 0.039072 SxxxVD HceeEE 58.723.5 333.5  7.513806 6.4629e−14 1.00000 N 0.176012 0.070611 ExxxAEHhhhHH 82.6 37.8 768.2  7.460296 8.0982e−14 1.00000 N 0.107524 0.049269KxxxLD HhccCC 25.2 6.4 158.0  7.548711 1.0095e−13 1.00000 N 0.1594940.040754 KxxxCK EeecCC 17.6 1.7 48.7 12.382741 1.5752e−13 1.00000 B0.361396 0.035054 CxxxYR HhhhHC 10.0 0.4 12.5 15.304518 1.7261e−131.00000 B 0.800000 0.032492 RxxxGL HhhhCC 28.6 8.1 176.7  7.3935682.7275e−13 1.00000 N 0.161856 0.045701 QxxxCW CcccHH 7.9 0.1 20.225.982292 3.1500e−13 1.00000 B 0.391089 0.004492 AxxxGK CcccCH 14.4 1.093.3 13.642109 8.6294e−13 1.00000 B 0.154341 0.010485 ExxxAL HhhhHC 32.210.0 257.3  7.160501 1.2869e−12 1.00000 N 0.125146 0.038867 PxxxSACceeEE 21.1 5.1 180.5  7.181197 1.7416e−12 1.00000 N 0.116898 0.028284DxxxNG CcccCC 41.8 14.9 391.2  7.084546 1.7924e−12 1.00000 N 0.1068510.038196 GxxxSA CcchHH 24.6 6.6 185.4  7.117102 2.2711e−12 1.00000 N0.132686 0.035702 RxxxDS HhheCC 16.7 1.8 45.2 11.428338 2.6297e−121.00000 B 0.369469 0.039275 SxxxNT CcccHH 12.5 0.8 23.9 12.9251103.2732e−12 1.00000 B 0.523013 0.035277 QxxxGK CcccCH 13.5 0.9 58.513.107957 4.1790e−12 1.00000 B 0.230769 0.015965 RxxxTG EeccCC 24.8 6.9127.8  7.018198 4.4794e−12 1.00000 N 0.194053 0.053883 GxxxDF EeccEE25.3 7.0 248.3  6.995039 5.0997e−12 1.00000 N 0.101893 0.028291 DxxxGSHhhhCC 20.9 3.3 65.1  9.930092 8.3751e−12 1.00000 B 0.321045 0.050797CxxxVG CcccCH 6.8 0.1 20.0 26.127329 1.0463e−11 1.00000 B 0.3400000.003332 SxxxGC EeccCC 15.3 1.4 138.8 11.769743 1.3088e−11 1.00000 B0.110231 0.010141 VxxxCI HhccCH 4.0 0.0 6.5 53.088891 1.3520e−11 1.00000B 0.615385 0.000872 ExxxSK HhhhHH 43.5 16.6 292.1  6.778914 1.4388e−111.00000 N 0.148922 0.056980 QxxxKT CcccHH 10.2 0.5 24.8 13.4235523.5602e−11 1.00000 B 0.411290 0.021381 AxxxGA HhhhCC 26.9 8.1 515.8 6.675596 4.0624e−11 1.00000 N 0.052152 0.015659 WxxxYA CcccHH 5.0 0.05.3 25.164503 4.1132e−11 1.00000 B 0.943396 0.007387 NxxxDK CeeeEE 29.89.8 140.6  6.628627 5.1332e−11 1.00000 N 0.211949 0.069648 FxxxLT HhhhHH24.0 6.8 425.0  6.631623 6.0285e−11 1.00000 N 0.056471 0.016048 AxxxGLHhhhCC 28.1 8.8 473.3  6.596022 6.5719e−11 1.00000 N 0.059370 0.018507NxxxGG CchhHC 9.3 0.5 16.8 13.308464 9.4341e−11 1.00000 B 0.5535710.027028 RxxxTD HcccCC 22.6 4.5 69.1  8.886497 9.5799e−11 1.00000 B0.327062 0.064487 KxxxCH HcccCC 10.6 0.7 19.9 12.354502 9.7646e−111.00000 B 0.532663 0.033601 SxxxGR CcccCH 12.7 1.0 40.8 11.5227911.0549e−10 1.00000 B 0.311275 0.025718 SxxxCW CcecHH 5.7 0.0 11.527.570955 1.2129e−10 1.00000 B 0.495652 0.003675 RxxxAE HhhhHH 57.2 25.4630.5  6.432535 1.2154e−10 1.00000 N 0.090722 0.040326 LxxxGV HhhhCC23.0 6.6 445.9  6.430108 2.2726e−10 1.00000 N 0.051581 0.014805 YxxxNREcccEE 19.8 5.4 85.3  6.438949 2.5510e−10 1.00000 N 0.232122 0.062882PxxxGK CcccCH 20.8 3.6 194.8  9.202084 2.5628e−10 1.00000 B 0.1067760.018331 QxxxYG CcccHH 13.3 1.4 40.0 10.338918 3.4539e−10 1.00000 B0.332500 0.034432 MxxxKF HcccCE 7.5 0.2 14.3 15.600641 4.0462e−101.00000 B 0.524476 0.015462 PxxxAL CchhHC 12.4 1.2 28.2 10.3207804.9428e−10 1.00000 B 0.439716 0.043459 QxxxCH HhhhHH 13.0 1.5 31.0 9.683104 6.3845e−10 1.00000 B 0.419355 0.047912 AxxxNF CcccCE 8.6 0.431.7 13.879215 8.1895e−10 1.00000 B 0.271293 0.011254 NxxxNR HhchHH 13.91.6 49.3  9.721101 1.0469e−09 1.00000 B 0.281947 0.033353 NxxxLM CcccCE5.0 0.1 6.3 19.458847 1.0490e−09 1.00000 B 0.793651 0.010316 RxxxGLCeccEC 6.2 0.2 6.0 13.456025 1.0888e−09 1.00000 B 1.033333 0.032074NxxxTT CcchHH 15.8 2.3 52.5  9.154042 1.1764e−09 1.00000 B 0.3009520.043434 KxxxQK EeccCC 8.2 0.5 9.5 10.982772 1.2202e−09 1.00000 B0.863158 0.054473 KxxxGK HhhhCC 30.7 11.1 167.2  6.107252 1.3267e−091.00000 N 0.183612 0.066190 RxxxGL HhhcCC 21.0 6.1 160.0  6.1566511.3396e−09 1.00000 N 0.131250 0.038087 ExxxAQ HhhhHH 43.6 18.2 430.8 6.069188 1.3445e−09 1.00000 N 0.101207 0.042332 RxxxGK HhhhCC 20.0 5.892.2  6.130584 1.6557e−09 1.00000 N 0.216920 0.062441 ExxxSR HhhhHH 34.513.2 256.4  6.044594 1.7844e−09 1.00000 N 0.134555 0.051287 MxxxRNHhhhCC 15.6 2.2 66.5  9.152082 1.8995e−09 1.00000 B 0.234586 0.033281GxxxAH ChhhHH 11.0 1.0 33.0 10.168580 2.0150e−09 1.00000 B 0.3333330.030234 HxxxGK CcccCH 9.0 0.5 49.3 11.829852 2.3778e−09 1.00000 B0.182556 0.010535 NxxxSR HhhcCH 11.2 1.1 22.1  9.635067 2.6454e−091.00000 B 0.506787 0.051948 AxxxQK HhhhCE 18.1 3.5 52.2  8.1573272.7384e−09 1.00000 B 0.346743 0.066142 QxxxGI HhhhCC 19.5 5.6 117.8 5.976186 4.1929e−09 1.00000 N 0.165535 0.047922 CxxxIG CcccCH 4.8 0.012.4 27.010872 4.6438e−09 1.00000 B 0.387097 0.002520 ExxxSK EcccCE 14.42.0 50.5  8.850457 5.1816e−09 1.00000 B 0.285149 0.040279 SxxxSL HhhhHC17.8 3.1 114.3  8.385299 5.7237e−09 1.00000 B 0.155731 0.027490 GxxxKTCcccHH 18.5 3.4 134.6  8.307329 5.8961e−09 1.00000 B 0.137444 0.025205RxxxQR HhhhHH 33.7 13.2 228.4  5.794345 7.8947e−09 1.00000 N 0.1475480.057959 KxxxPG HhhcCC 28.5 10.4 157.6  5.811554 7.9723e−09 1.00000 N0.180838 0.065945 AxxxCH CchhHH 6.0 0.1 5.0 14.128524 8.7129e−09 1.00000B 1.200000 0.024436 RxxxGG HhhhCC 20.3 4.5 85.3  7.694509 9.8975e−091.00000 B 0.237984 0.052377 AxxxRH HhhhHH 29.4 10.9 245.6  5.7498601.1049e−08 1.00000 N 0.119707 0.044253 CxxxIG CcccCC 9.5 0.7 40.610.749424 1.1320e−08 1.00000 B 0.233990 0.016851

TABLE 22 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityGxxKxT CccHhH 83.1 9.8 353.1 23.760777  1.9863e−123 1.00000 N 0.2353440.027728 TxxGxT CccChH 46.6 5.5 140.5 17.925581 1.8308e−70 1.00000 N0.331673 0.038978 VxxKxG EccCcC 41.9 6.3 138.2 14.475018 1.6458e−461.00000 N 0.303184 0.045794 SxxVxK CeeEeE 65.3 16.6 303.8 12.3093231.9144e−34 1.00000 N 0.214944 0.054555 QxxGxG CccChH 34.0 2.7 61.519.639877 3.0967e−30 1.00000 B 0.552846 0.043273 DxxGxG CccCcC 95.4 33.31003.2 10.953878 8.3945e−28 1.00000 N 0.095096 0.033166 CxxGxT CccCcC36.2 3.3 126.6 18.275052 5.0452e−27 1.00000 B 0.285940 0.026253 RxxDxDHhhCcC 36.6 7.6 188.0 10.735002 2.5428e−26 1.00000 N 0.194681 0.040444DxxGxT CccChH 25.3 1.6 63.1 19.072943 7.2871e−24 1.00000 B 0.4009510.025131 PxxLxV CceEeE 32.3 6.5 409.9 10.154812 1.1669e−23 1.00000 N0.078800 0.015954 TxxDxK EeeEeE 71.3 24.2 396.7  9.891898 6.4050e−231.00000 N 0.179733 0.060932 PxxNxG CeeCcC 15.5 0.3 24.8 26.8297016.7903e−23 1.00000 B 0.625000 0.013072 DxxVxK CccCcH 23.6 1.5 120.518.328477 4.2756e−21 1.00000 B 0.195851 0.012242 LxxLxT HhhChH 14.7 0.421.1 23.070139 2.0329e−20 1.00000 B 0.696682 0.018575 FxxHxA CccHhH 11.60.2 19.0 27.924333 7.9156e−19 1.00000 B 0.610526 0.008899 RxxGxG CccChH24.2 2.4 63.5 14.513003 1.7368e−18 1.00000 B 0.381102 0.037058 LxxNxMCchHhH 18.1 1.0 44.6 17.173637 1.8356e−18 1.00000 B 0.405830 0.022712SxxGxT CccChH 30.5 4.0 129.8 13.540361 2.3842e−18 1.00000 B 0.2349770.030525 NxxKxT CccHhH 23.8 2.3 62.4 14.345065 6.0409e−18 1.00000 B0.381410 0.037298 SxxKxD HceEeE 57.0 19.8 313.1  8.642784 7.5321e−181.00000 N 0.182050 0.063201 YxxGxT HhcCcC 22.1 2.2 65.5 13.5866301.4379e−16 1.00000 B 0.337405 0.033843 CxxGxG CccCcH 10.3 0.1 51.327.308055 1.8238e−16 1.00000 B 0.200780 0.002706 DxxGxP HhhCcC 33.8 9.3183.0  8.241246 3.4292e−16 1.00000 N 0.184699 0.050855 LxxKxY HhhCcC22.3 2.4 89.2 13.024128 1.5264e−15 1.00000 B 0.250000 0.026898 GxxKxSCccHhH 24.1 2.9 119.6 12.606859 1.6128e−15 1.00000 B 0.201505 0.024235ExxGxS HhhCcC 35.4 10.4 185.6  7.959755 3.0861e−15 1.00000 N 0.1907330.056187 KxxFxV HhcCcH 11.6 0.4 15.8 17.893079 3.6601e−15 1.00000 B0.734177 0.025436 LxxAxK CccCcH 14.8 0.8 60.2 15.943519 9.6061e−151.00000 B 0.245847 0.013008 RxxMxS HhhEcC 16.7 1.3 42.2 13.8018931.5849e−14 1.00000 B 0.395735 0.030483 MxxFxF HccCcE 7.5 0.1 12.030.033887 3.6712e−14 1.00000 B 0.625000 0.005138 MxxCxL EecCcC 7.0 0.110.0 26.697096 7.8298e−14 1.00000 B 0.700000 0.006788 YxxNxQ CccCcC 22.93.2 83.7 11.126181 1.4659e−13 1.00000 B 0.273596 0.038784 KxxGxD HhcCcC46.7 17.0 284.7  7.415308 1.5458e−13 1.00000 N 0.164032 0.059814 AxxGxPHhcCcC 32.9 9.9 247.6  7.451189 1.5600e−13 1.00000 N 0.132876 0.040039KxxGxN HhcCcC 33.4 10.3 186.4  7.375182 2.6922e−13 1.00000 N 0.1791850.055503 SxxGxS CccChH 26.0 4.6 127.5 10.143807 8.1010e−13 1.00000 B0.203922 0.036176 NxxCxN EecCcC 14.5 1.1 43.0 12.726677 1.5589e−121.00000 B 0.337209 0.026349 AxxKxT CccHhH 14.5 1.2 45.7 12.5484212.4406e−12 1.00000 B 0.317287 0.025375 GxxGxC CccCcH 13.3 0.9 44.912.905411 3.8622e−12 1.00000 B 0.296214 0.020874 SxxAxW CceChH 5.2 0.05.0 29.896993 5.3267e−12 1.00000 B 1.040000 0.005563 KxxGxP HhhCcC 39.714.3 276.0  6.907485 6.3677e−12 1.00000 N 0.143841 0.051742 RxxGxAHhhCcC 21.2 5.4 114.5  6.985745 6.6680e−12 1.00000 N 0.185153 0.046994RxxDxS EccCcC 20.5 5.1 138.7  6.971130 7.6462e−12 1.00000 N 0.1478010.036621 ExxPxD HhcCcC 20.1 5.1 88.6  6.882766 1.4270e−11 1.00000 N0.226862 0.057140 RxxGxP HhhCcC 35.0 12.1 274.9  6.707417 2.6783e−111.00000 N 0.127319 0.044184 NxxGxS CecCeC 18.6 2.8 49.7  9.7841633.5481e−11 1.00000 B 0.374245 0.055768 ExxGxS HhcCcC 24.9 7.3 129.6 6.682720 4.2194e−11 1.00000 N 0.192130 0.056545 SxxWxS CccCcC 23.6 6.7200.2  6.644325 5.6746e−11 1.00000 N 0.117882 0.033448 RxxGxN HhcCcC27.5 8.6 166.0  6.600575 6.5622e−11 1.00000 N 0.165663 0.051959 SxxIxRCccCcH 9.7 0.4 26.0 14.293879 6.8602e−11 1.00000 B 0.373077 0.016455GxxFxI EccEeE 8.2 0.3 14.4 14.787675 8.3777e−11 1.00000 B 0.5694440.020271 NxxVxK CeeEeE 31.3 10.6 203.1  6.545306 8.4370e−11 1.00000 N0.154111 0.052072 TxxLxK CccCcH 12.8 1.1 41.4 11.514712 9.3815e−111.00000 B 0.309179 0.025747 ExxGxP HhcCcC 32.8 11.5 226.1  6.4502921.4987e−10 1.00000 N 0.145069 0.050838 MxxSxN HhhHcC 14.4 1.5 54.610.544362 1.5677e−10 1.00000 B 0.263736 0.028063 CxxNxC EccCcC 7.6 0.227.4 17.711018 1.6978e−10 1.00000 B 0.277372 0.006453 KxxGxN HhhCcC 32.111.2 196.9  6.425281 1.7880e−10 1.00000 N 0.163027 0.056929 SxxIxRCccChH 7.5 0.2 22.9 16.857018 2.8617e−10 1.00000 B 0.327511 0.008281ExxLxY HhhHhC 17.0 2.5 69.1  9.239619 4.0465e−10 1.00000 B 0.2460200.036788 GxxKxA CccHhH 21.1 3.9 165.6  8.815648 4.6376e−10 1.00000 B0.127415 0.023544 RxxTxK HhcCcC 14.5 1.9 33.2  9.273239 9.5076e−101.00000 B 0.436747 0.058635 SxxTxC HhhCcE 5.3 0.0 4.0 26.7406849.5757e−10 1.00000 B 1.325000 0.005563 RxxGxV HhhCcC 19.6 3.6 103.7 8.613509 1.4059e−09 1.00000 B 0.189007 0.034542 ExxGxV HhhCcC 21.1 4.3110.4  8.311882 1.4089e−09 1.00000 B 0.191123 0.038646 AxxGxA HhhCcC20.9 6.1 152.0  6.130139 1.5782e−09 1.00000 N 0.137500 0.040030 TxxGxTEecCeE 29.0 10.2 184.0  6.076901 1.6537e−09 1.00000 N 0.157609 0.055253QxxTxK CccCcH 7.5 0.2 21.1 14.590222 1.7420e−09 1.00000 B 0.3554500.011843 PxxSxK CccCcH 11.0 0.9 71.6 10.601684 2.0925e−09 1.00000 B0.153631 0.012799 NxxPxR HhcHhH 13.9 1.8 59.3  9.320763 2.9671e−091.00000 B 0.234401 0.029523 DxxTxT EccCcE 19.9 3.9 104.8  8.2021273.2719e−09 1.00000 B 0.189885 0.037557 PxxGxS HhhCeC 7.4 0.4 8.511.674578 3.5192e−09 1.00000 B 0.870588 0.044539 ExxGxL HhcCcC 20.8 4.3112.8  8.112994 3.5599e−09 1.00000 B 0.184397 0.038122 AxxGxS HhhCcC26.8 9.2 190.0  5.946894 3.7813e−09 1.00000 N 0.141053 0.048433 QxxCxSCccCeC 5.1 0.1 38.9 20.782682 3.9101e−09 1.00000 B 0.131105 0.001515LxxSxK CccCcH 9.0 0.6 47.6 11.386026 4.1886e−09 1.00000 B 0.1890760.011690 FxxAxN CchHhH 7.8 0.3 17.0 12.974151 4.3718e−09 1.00000 B0.458824 0.019855 RxxGxE HhcCcC 30.2 11.2 186.3  5.834341 6.7156e−091.00000 N 0.162104 0.060330 AxxGxP HhhCcC 32.6 12.5 323.5  5.8187346.9638e−09 1.00000 N 0.100773 0.038516 NxxDxD HhhCcC 14.0 2.0 57.2 8.641401 7.8927e−09 1.00000 B 0.244755 0.034942 RxxGxP HhcCcC 27.1 9.6187.1  5.799118 8.8328e−09 1.00000 N 0.144842 0.051307 CxxGxM HhcCcH 8.00.4 26.4 11.413436 8.9920e−09 1.00000 B 0.303030 0.016879 LxxGxR HhcCcC19.7 5.8 175.5  5.837346 9.1774e−09 1.00000 N 0.112251 0.033250 DxxExGEeeEcC 15.2 2.5 65.7  8.298279 1.2842e−08 1.00000 B 0.231355 0.037315QxxSxW CccChH 6.1 0.2 25.7 14.525392 1.3369e−08 1.00000 B 0.2373540.006532 IxxGxL HhhCcC 16.6 2.8 119.7  8.281164 1.3631e−08 1.00000 B0.138680 0.023654 FxxMxR ChhHhH 9.7 0.8 22.6 10.065010 1.3976e−081.00000 B 0.429204 0.035808 LxxAxK EccCcH 7.0 0.3 14.5 11.6455681.4353e−08 1.00000 B 0.482759 0.023123 LxxPxY CccCcC 20.5 6.3 212.2 5.742644 1.5087e−08 1.00000 N 0.096607 0.029693 ExxGxW CccCcE 9.0 0.732.0 10.221785 1.5374e−08 1.00000 B 0.281250 0.021165 NxxCxS CceEeC 5.50.1 5.5 14.257524 1.6946e−08 1.00000 B 1.000000 0.026344 GxxPxW CceCcC6.0 0.3 7.0 11.416331 1.8807e−08 1.00000 B 0.857143 0.037489 RxxGxSHhcCcC 22.0 7.2 126.2  5.687773 1.9453e−08 1.00000 N 0.174326 0.056971AxxGxT HhcCcC 20.6 6.5 145.6  5.653943 2.4711e−08 1.00000 N 0.1414840.044679 DxxExL EhhHhH 13.6 1.9 70.0  8.562336 2.4756e−08 1.00000 B0.194286 0.027355 ExxGxE HhhCcC 33.2 13.4 223.9  5.576582 2.7286e−081.00000 N 0.148280 0.059866 KxxHxY HhhCcC 7.0 0.4 11.3 10.4603233.2212e−08 1.00000 B 0.619469 0.036433 PxxSxE CccChH 34.3 14.1 270.2 5.539452 3.2852e−08 1.00000 N 0.126943 0.052072 GxxTxY CccEeE 18.5 5.6135.9  5.610971 3.4396e−08 1.00000 N 0.136130 0.040853 ExxGxR HhcCcC18.1 5.4 95.5  5.613533 3.4784e−08 1.00000 N 0.189529 0.056691

TABLE 23 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityTxxGKT CccCHH 42.4 2.6 117.2 24.985498 4.7047e−39 1.00000 B 0.3617750.022146 SxxVDK CeeEEE 59.1 13.1 253.5 13.080308 1.3690e−38 1.00000 N0.233136 0.051524 DxxGKT CccCHH 24.3 0.5 45.9 35.121431 5.7625e−361.00000 B 0.529412 0.010137 TxxDKK EeeEEE 69.9 18.8 364.0 12.1056232.0737e−33 1.00000 N 0.192033 0.051630 GxxKTT CccHHH 37.1 3.0 141.819.967429 1.5635e−29 1.00000 B 0.261636 0.021032 YxxNFQ CccCCC 18.6 0.422.6 30.533644 3.4603e−29 1.00000 B 0.823009 0.016043 GxxKST CccHHH 30.92.1 110.3 19.885548 1.1670e−26 1.00000 B 0.280145 0.019346 QxxGLG CccCHH16.0 0.4 16.7 24.595142 1.4620e−25 1.00000 B 0.958084 0.024661 DxxVGKCccCCH 20.6 0.6 102.6 24.935978 2.1888e−24 1.00000 B 0.200780 0.006281LxxAGK CccCCH 14.8 0.2 46.4 35.352560 4.6640e−24 1.00000 B 0.3189660.003704 SxxKVD HceEEE 56.5 16.4 313.0 10.172335 4.8080e−24 1.00000 N0.180511 0.052395 SxxIGR CccCCH 9.7 0.0 14.7 71.755345 7.9503e−241.00000 B 0.659864 0.001240 SxxGKS CccCHH 25.0 1.5 91.5 19.2600121.8449e−23 1.00000 B 0.273224 0.016527 SxxGNT CccCHH 12.5 0.1 11.031.354824 3.0442e−22 1.00000 B 1.136364 0.011065 LxxNVM CchHHH 18.1 0.730.9 20.921107 3.8340e−22 1.00000 B 0.585761 0.022891 RxxMDS HhhECC 16.70.4 42.2 24.919014 6.1180e−22 1.00000 B 0.395735 0.010205 CxxNIC EccCCC7.0 0.0 12.0 90.555035 5.9489e−21 1.00000 B 0.583333 0.000497 NxxKTTCccHHH 15.8 0.5 24.1 20.868377 5.3869e−20 1.00000 B 0.655602 0.022683PxxNIG CeeCCC 14.3 0.1 10.3 29.833145 6.0708e−20 1.00000 B 1.3883500.011440 DxxGDG CccCCC 32.8 7.6 245.6 9.251579 6.0747e−20 1.00000 N0.133550 0.031090 VxxKNG EccCCC 26.6 2.8 57.3 14.434463 1.7747e−191.00000 B 0.464223 0.049723 CxxGIG CccCCC 6.3 0.0 11.9 112.4133012.0360e−19 1.00000 B 0.529412 0.000264 YxxGRT HhcCCC 18.3 1.0 35.417.340206 5.1270e−19 1.00000 B 0.516949 0.028879 SxxIGR CccCHH 7.3 0.020.2 61.430311 4.6706e−18 1.00000 B 0.361386 0.000697 NxxVDK CeeEEE 29.87.1 135.8 8.714799 7.8056e−18 1.00000 N 0.219440 0.052559 SxxVGR CccCHH8.3 0.0 20.1 43.587327 9.6557e−18 1.00000 B 0.412935 0.001792 NxxVDNCeeECC 1.0 0.0 1.0 5.018033 1.0678e−16 1.00000 B 1.000000 0.038196QxxFHI HhhHCC 1.6 0.0 1.0 5.358042 1.0729e−16 1.00000 B 1.6000000.033660 YxxIHA EecCCC 1.5 0.0 1.0 6.463791 1.0843e−16 1.00000 B1.500000 0.023375 DxxRFV CccCCE 1.0 0.0 1.0 6.799182 1.0867e−16 1.00000B 1.000000 0.021173 TxxVFE CccEEC 1.0 0.0 1.0 9.900521 1.0990e−161.00000 B 1.000000 0.010099 GxxDNG CceEEE 1.0 0.0 1.0 10.1538861.0996e−16 1.00000 B 1.000000 0.009606 DxxGNG CccCCC 30.0 4.5 174.512.117828 3.3659e−16 1.00000 B 0.171920 0.025984 AxxVGK CccCCH 8.6 0.132.0 33.752156 1.0516e−15 1.00000 B 0.268750 0.002003 PxxSGK CccCCH 11.00.2 54.7 21.809359 1.3203e−15 1.00000 B 0.201097 0.004466 KxxFTV HhcCCH11.1 0.4 14.1 17.687177 1.7765e−15 1.00000 B 0.787234 0.026782 RxxTFKHhcCCC 11.0 0.5 11.5 15.520720 2.5051e−15 1.00000 B 0.956522 0.041692GxxKTS CccHHH 13.9 0.6 33.5 16.756306 2.7900e−15 1.00000 B 0.4149250.019061 QxxGKT CccCHH 10.2 0.2 23.0 21.950729 3.1726e−15 1.00000 B0.443478 0.009090 DxxTGK CccCCH 8.0 0.1 31.4 29.149732 8.1205e−151.00000 B 0.254777 0.002360 LxxSGK CccCCH 9.0 0.1 31.2 24.2220341.0197e−14 1.00000 B 0.288462 0.004312 QxxGYG CccCHH 12.3 0.6 20.115.259162 4.3218e−14 1.00000 B 0.611940 0.030129 MxxCTL EecCCC 7.0 0.19.0 26.919571 4.4228e−14 1.00000 B 0.777778 0.007425 QxxSCW CccCHH 6.10.0 20.2 40.736633 6.6470e−14 1.00000 B 0.301980 0.001103 MxxFKF HccCCE7.5 0.1 10.7 26.539741 1.4215e−13 1.00000 B 0.700935 0.007362 GxxKSACccHHH 14.5 0.9 56.2 14.356408 1.4566e−13 1.00000 B 0.258007 0.016205LxxKDY HhhCCC 12.4 0.8 17.5 13.258420 4.4705e−13 1.00000 B 0.7085710.045827 RxxGIG CccCHH 10.2 0.4 15.1 15.563661 4.7518e−13 1.00000 B0.675497 0.026947 SxxACW CceCHH 5.2 0.0 4.0 67.545729 5.8875e−13 1.00000B 1.300000 0.000876 GxxIMS CccHHH 5.0 0.0 5.8 38.483793 9.0813e−131.00000 B 0.862069 0.002899 CxxGVG CccCCH 5.8 0.0 18.8 42.9836191.8140e−12 1.00000 B 0.308511 0.000963 KxxACK EeeCCC 15.3 1.4 42.011.769566 3.0198e−12 1.00000 B 0.364286 0.034205 GxxGKT CccCHH 16.5 1.7115.5 11.634197 7.0138e−12 1.00000 B 0.142857 0.014306 NxxSGK CccCCH 5.50.0 10.0 35.698627 9.1312e−12 1.00000 B 0.550000 0.002359 QxxTGK CccCCH7.5 0.1 16.1 20.225448 1.5596e−11 1.00000 B 0.465839 0.008308 IxxYTPEccCCC 9.6 0.3 54.6 16.103991 2.2522e−11 1.00000 B 0.175824 0.006102NxxPNR HhcHHH 13.9 1.2 47.4 11.480225 3.1658e−11 1.00000 B 0.2932490.026318 MxxSRN HhhHCC 13.4 1.2 42.0 11.445113 4.7252e−11 1.00000 B0.319048 0.027951 NxxCKN EecCCC 13.3 1.2 43.0 11.287293 6.3736e−111.00000 B 0.309302 0.027552 SxxAGN EccCCC 7.0 0.2 7.1 13.9938096.7483e−11 1.00000 B 0.985915 0.034010 AxxKTT CccHHH 9.0 0.4 21.513.833100 7.3110e−11 1.00000 B 0.418605 0.018337 ExxVGK CccCCH 7.7 0.234.6 18.607804 9.4920e−11 1.00000 B 0.222543 0.004762 VxxGCI HhcCCH 4.00.0 6.5 40.995245 1.0625e−10 1.00000 B 0.615385 0.001460 CxxGIG CccCCH4.5 0.0 12.4 45.567392 1.0818e−10 1.00000 B 0.362903 0.000784 RxxPFNEecCCC 7.5 0.1 6.0 16.214277 1.2341e−10 1.00000 B 1.250000 0.022313SxxGKT CccCHH 14.0 1.4 83.3 10.619350 1.7092e−10 1.00000 B 0.1680670.017123 KxxACH HccCCC 7.0 0.1 6.0 15.752097 1.7322e−10 1.00000 B1.166667 0.023610 TxxGKS CccCHH 10.6 0.6 35.1 12.475499 2.4413e−101.00000 B 0.301994 0.018470 LxxICR CccCCH 4.0 0.0 7.8 37.1970582.9087e−10 1.00000 B 0.512821 0.001476 SxxWPS CccCCC 19.8 5.3 162.26.396654 3.2879e−10 1.00000 N 0.122072 0.032719 RxxLPE HhhCCC 11.6 0.930.6 11.271642 3.4023e−10 1.00000 B 0.379085 0.030226 RxxGLG CccCHH 6.30.1 10.8 18.190253 4.2775e−10 1.00000 B 0.583333 0.010816 KxxSPQ HhcCCC5.2 0.1 7.1 21.929565 5.3759e−10 1.00000 B 0.732394 0.007812 VxxGKTCccCHH 10.0 0.6 44.3 11.867670 5.9907e−10 1.00000 B 0.225734 0.014269DxxGGG ChhHCC 9.8 0.6 19.9 11.917268 6.6472e−10 1.00000 B 0.4924620.030812 PxxGKG CccCHH 11.0 0.9 38.6 10.839654 8.0255e−10 1.00000 B0.284974 0.023067 GxxLGR CccHHH 7.0 0.2 10.9 13.800966 8.0725e−101.00000 B 0.642202 0.022484 LxxGMV CeeEEE 3.3 0.0 8.2 68.0879599.9956e−10 1.00000 B 0.402439 0.000286 LxxAGK EccCCH 7.0 0.2 13.513.633148 1.6346e−09 1.00000 B 0.518519 0.018502 TxxGVH CceEEE 5.3 0.04.5 26.658583 1.9226e−09 1.00000 B 1.177778 0.006292 SxxSLS EccEEE 19.55.5 109.4 6.102942 1.9949e−09 1.00000 N 0.178245 0.050489 TxxIGE EecCCE6.3 0.2 6.3 13.360594 2.1393e−09 1.00000 B 1.000000 0.034090 GxxGSCCccCCH 7.1 0.2 32.1 14.576219 2.1556e−09 1.00000 B 0.221184 0.006981GxxKSS CccHHH 10.2 0.8 37.0 10.871965 2.5245e−09 1.00000 B 0.2756760.020771 GxxKSC CccHHH 8.5 0.4 19.9 12.276595 2.8204e−09 1.00000 B0.427136 0.022147 CxxGGW CccCHH 3.0 0.0 10.9 55.906034 2.9320e−091.00000 B 0.275229 0.000264 DxxDIG CccCHH 6.0 0.2 9.5 14.7147802.9576e−09 1.00000 B 0.631579 0.016864 AxxGDS CccCCC 10.8 0.8 106.311.008754 3.4357e−09 1.00000 B 0.101599 0.007781 WxxGYA CccCHH 5.0 0.04.0 22.536110 3.7289e−09 1.00000 B 1.250000 0.007814 KxxRME CccCCC 7.40.3 17.5 13.498147 3.7508e−09 1.00000 B 0.422857 0.016148 QxxGIM CccCHH4.8 0.0 7.0 25.824874 3.9991e−09 1.00000 B 0.685714 0.004889 KxxHPYHhhCCC 6.5 0.3 6.6 12.654223 5.5331e−09 1.00000 B 0.984848 0.038395NxxCGS CceEEC 5.5 0.1 5.0 14.589457 6.3685e−09 1.00000 B 1.1000000.022951 GxxHDI CccCCH 6.0 0.3 6.1 11.668890 6.4387e−09 1.00000 B0.983607 0.041485 GxxKTF CccHHH 8.0 0.5 17.8 11.183882 6.8420e−091.00000 B 0.449438 0.026180 VxxLMV EeeEEE 3.0 0.0 4.0 42.6291677.5384e−09 1.00000 B 0.750000 0.001236 LxxFMR EccCCC 5.0 0.1 11.017.765741 7.6538e−09 1.00000 B 0.454545 0.007029 KxxGLD HhcCCC 15.6 2.568.8 8.533480 8.1840e−09 1.00000 B 0.226744 0.035744 GxxGFT HhhCCH 12.91.7 33.5 8.805582 8.4299e−09 1.00000 B 0.385075 0.050848

TABLE 24 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityGxGxxT CcChhH 95.5 16.6 530.8 19.647819 3.4828e−85 1.00000 N 0.1799170.031337 VxCxxG EcCccC 40.5 1.7 79.3 30.256305 1.7042e−45 1.00000 B0.510719 0.021207 ExIxxW CcChhH 22.8 0.2 24.5 51.610706 8.9399e−451.00000 B 0.930612 0.007893 SxKxxK CeEeeE 64.0 14.8 237.7 13.1797693.3609e−39 1.00000 N 0.269247 0.062429 TxTxxT CcCchH 32.0 1.2 56.528.650551 7.1879e−39 1.00000 B 0.566372 0.020916 GxSxxE CcChhH 92.3 27.3563.9 12.762018 4.6873e−37 1.00000 N 0.163682 0.048374 LxPxxR CcHhhH39.9 7.4 228.2 12.087836 5.8061e−33 1.00000 N 0.174847 0.032646 GxPxxQCcChhH 38.5 7.2 136.1 11.993530 1.9062e−32 1.00000 N 0.282880 0.052856NxTxxE CcChhH 54.0 13.3 264.7 11.434346 7.0416e−30 1.00000 N 0.2040050.050340 GxTxxQ CcChhH 51.1 12.8 261.6 10.949601 1.6032e−27 1.00000 N0.195336 0.049082 RxIxxF EeEccC 32.0 3.0 66.9 16.977592 3.0617e−251.00000 B 0.478326 0.045546 GxGxxS CcChhH 41.3 4.9 257.3 16.4982673.7587e−25 1.00000 B 0.160513 0.019237 PxWxxG CeEccC 14.5 0.2 18.732.157769 9.6205e−25 1.00000 B 0.775401 0.010689 SxAxxR ChHhhH 47.9 13.4257.1 9.692430 6.3584e−22 1.00000 N 0.186309 0.052044 QxPxxL EeCceE 34.67.9 344.0 9.568532 3.0272e−21 1.00000 N 0.100581 0.023093 DxAxxT CcCchH22.1 1.4 57.2 17.870923 3.8331e−21 1.00000 B 0.386364 0.024086 NxGxxTCcChhH 25.8 2.5 65.9 15.098624 1.3414e−19 1.00000 B 0.391502 0.037617LxExxI CcHhhH 31.2 7.4 297.3 8.889427 1.6173e−18 1.00000 N 0.1049450.024787 TxVxxK EeEeeE 70.3 26.3 562.7 8.776302 2.0407e−18 1.00000 N0.124933 0.046795 LxExxR CcHhhH 29.6 6.8 193.1 8.870479 2.0553e−181.00000 N 0.153288 0.035373 DxGxxK CcCccH 25.6 2.6 108.4 14.3335056.4194e−18 1.00000 B 0.236162 0.024277 LxPxxQ CcHhhH 26.4 5.8 169.78.748374 6.9214e−18 1.00000 N 0.155569 0.033949 ExSxxE CcChhH 46.7 14.6297.5 8.631726 9.6940e−18 1.00000 N 0.156975 0.048973 YxSxxT HhCccC 20.31.6 51.4 14.976341 2.1046e−17 1.00000 B 0.394942 0.031285 GxSxxN CeChhH21.5 2.0 57.9 14.186410 6.8792e−17 1.00000 B 0.371330 0.033905 SxTxxDHcEeeE 58.2 21.1 334.4 8.334126 1.0029e−16 1.00000 N 0.174043 0.063172RxDxxY EeEecC 1.0 0.0 1.0 6.479049 1.0844e−16 1.00000 B 1.0000000.023268 GxSxxT CcChhH 25.9 5.9 139.5 8.404110 1.2643e−16 1.00000 N0.185663 0.042356 PxHxxL CcHhhC 12.9 0.5 18.3 18.181695 2.5192e−161.00000 B 0.704918 0.026188 DxAxxQ ChHhhH 30.4 7.9 151.2 8.2569383.4079e−16 1.00000 N 0.201058 0.051986 TxCxxC CcHhhH 14.7 0.9 13.514.119043 5.4430e−16 1.00000 B 1.088889 0.063426 GxSxxA CcChhH 30.1 7.8260.9 8.142754 8.5659e−16 1.00000 N 0.115370 0.029738 TxAxxE ChHhhH 42.113.3 254.5 8.093575 9.1094e−16 1.00000 N 0.165422 0.052386 CxAxxG CcCccH11.6 0.3 44.1 22.129643 9.5347e−16 1.00000 B 0.263039 0.005986 GxDxxQCcChhH 29.0 7.4 147.4 8.106973 1.1979e−15 1.00000 N 0.196744 0.050510SxYxxE ChHhhH 23.4 2.9 60.5 12.397158 1.2306e−15 1.00000 B 0.3867770.047559 CxNxxT CcCccC 21.3 2.3 79.4 12.866017 4.0656e−15 1.00000 B0.268262 0.028403 TxAxxK ChHhhH 33.7 9.7 179.1 7.910811 4.7461e−151.00000 N 0.188163 0.054259 SxSxxA CcChhH 28.4 7.3 190.0 7.9319194.8305e−15 1.00000 N 0.149474 0.038609 CxGxxY EeCccC 16.0 1.2 54.713.787800 2.6979e−14 1.00000 B 0.292505 0.021585 LxDxxR CcHhhH 24.5 6.0159.0 7.656071 4.7140e−14 1.00000 N 0.154088 0.038000 GxTxxD CcChhH 47.316.9 366.4 7.557245 5.3153e−14 1.00000 N 0.129094 0.046209 LxSxxR CcHhhH20.0 2.2 79.5 12.061536 5.7006e−14 1.00000 B 0.251572 0.028083 NxKxxKCeEeeE 32.2 9.6 154.0 7.535957 8.5785e−14 1.00000 N 0.209091 0.062307GxGxxA CcChhH 24.7 6.2 337.1 7.548724 1.0269e−13 1.00000 N 0.0732720.018245 SxVxxS CcCchH 21.3 2.6 98.9 11.741540 1.0710e−13 1.00000 B0.215369 0.026329 LxExxK CcHhhH 24.2 6.0 184.2 7.523785 1.2703e−131.00000 N 0.131379 0.032735 TxTxxE CcChhH 30.8 9.0 191.4 7.4686041.4651e−13 1.00000 N 0.160920 0.046846 SxGxxC EeCccC 15.5 1.0 147.614.198789 1.5326e−13 1.00000 B 0.105014 0.007073 GxSxxD CcChhH 52.0 19.9441.1 7.347550 2.3629e−13 1.00000 N 0.117887 0.045205 GxSxxQ CcChhH 32.59.9 203.2 7.392465 2.4290e−13 1.00000 N 0.159941 0.048517 FxVxxN CcHhhH9.0 0.2 14.7 17.947861 3.1447e−13 1.00000 B 0.612245 0.016469 DxAxxEChHhhH 48.7 18.3 339.8 7.304968 3.3650e−13 1.00000 N 0.143320 0.053861FxTxxR ChHhhH 13.6 1.1 20.2 12.530961 6.0951e−13 1.00000 B 0.6732670.052338 SxExxR ChHhhH 62.2 26.5 481.7 7.130862 1.0256e−12 1.00000 N0.129126 0.055033 SxAxxE ChHhhH 40.7 14.4 301.5 7.112073 1.5082e−121.00000 N 0.134992 0.047697 MxTxxF HcCccE 7.5 0.1 11.8 22.3567782.0200e−12 1.00000 B 0.635593 0.009346 RxSxxE CeEhhH 9.0 0.3 8.915.363457 2.1971e−12 1.00000 B 1.011236 0.036336 TxAxxQ ChHhhH 35.1 11.8204.9 6.994651 3.8335e−12 1.00000 N 0.171303 0.057525 NxTxxR HhChhH 13.91.1 47.4 12.497161 5.0108e−12 1.00000 B 0.293249 0.022727 NxSxxD CcChhH25.1 7.0 145.6 6.979942 5.7351e−12 1.00000 N 0.172390 0.048331 GxNxxECcChhH 35.9 12.3 268.7 6.879201 8.2900e−12 1.00000 N 0.133606 0.045839LxAxxR CcHhhH 23.3 4.1 144.3 9.678385 1.6775e−11 1.00000 B 0.1614690.028167 FxGxxA CcChhH 13.1 1.1 51.0 11.868621 2.5395e−11 1.00000 B0.256863 0.020630 QxRxxG CcCchH 11.8 0.9 20.3 11.983867 2.9355e−111.00000 B 0.581281 0.042817 SxGxxR CcCchH 13.2 1.0 69.8 12.0219122.9539e−11 1.00000 B 0.189112 0.014882 ExDxxG HhCccC 20.8 5.4 144.56.752501 3.2182e−11 1.00000 N 0.143945 0.037384 AxGxxT CcChhH 14.7 1.471.0 11.378940 3.7774e−11 1.00000 B 0.207042 0.019643 DxAxxR ChHhhH 33.911.7 212.5 6.651301 3.9842e−11 1.00000 N 0.159529 0.055269 GxDxxA CcChhH41.7 16.0 346.5 6.586367 5.2939e−11 1.00000 N 0.120346 0.046127 GxTxxECcChhH 54.9 23.8 506.5 6.546520 5.9175e−11 1.00000 N 0.108391 0.046894TxSxxE CcChhH 26.4 8.1 188.8 6.578130 7.8469e−11 1.00000 N 0.1398310.042863 PxTxxQ CcChhH 21.7 5.9 173.7 6.591601 8.7031e−11 1.00000 N0.124928 0.034126 TxDxxR CcHhhH 16.8 2.3 45.8 9.817220 9.5154e−111.00000 B 0.366812 0.050164 GxCxxC CcCccH 7.4 0.2 31.8 18.6504579.8742e−11 1.00000 B 0.232704 0.004772 SxAxxA ChHhhH 31.9 10.8 324.76.517178 9.9192e−11 1.00000 N 0.098245 0.033327 AxGxxK CcCccH 15.1 1.777.9 10.453088 1.1289e−10 1.00000 B 0.193838 0.021614 QxRxxE CcChhH 21.84.2 68.2 8.849948 1.4429e−10 1.00000 B 0.319648 0.061734 GxDxxE CcChhH36.8 13.7 254.3 6.426476 1.6131e−10 1.00000 N 0.144711 0.053792 NxAxxKChHhhH 23.7 7.1 137.1 6.437742 2.1271e−10 1.00000 N 0.172867 0.051429DxAxxD ChHhhH 28.7 9.5 168.1 6.409489 2.1528e−10 1.00000 N 0.1707320.056547 TxAxxR ChHhhH 26.0 8.1 178.9 6.402991 2.4282e−10 1.00000 N0.145333 0.045534 NxGxxK CcCccH 10.0 0.6 25.9 11.827359 3.0863e−101.00000 B 0.386100 0.024785 DxAxxA ChHhhH 40.7 16.0 424.8 6.3061703.2326e−10 1.00000 N 0.095810 0.037604 NxGxxS CcChhH 15.0 1.9 51.59.590943 4.1423e−10 1.00000 B 0.291262 0.037466 GxGxxI EcCeeE 12.5 1.147.7 10.879784 4.3984e−10 1.00000 B 0.262055 0.023487 NxGxxV ChHhhH 10.20.6 56.2 12.284253 4.6883e−10 1.00000 B 0.181495 0.010952 KxSxxE CcChhH34.8 13.0 249.7 6.189193 7.3797e−10 1.00000 N 0.139367 0.052226 CxGxxCEcCccC 7.5 0.2 22.1 15.600743 7.6434e−10 1.00000 B 0.339367 0.009952SxTxxE CcChhH 26.3 8.6 179.1 6.210132 7.9457e−10 1.00000 N 0.1468450.047823 TxGxxT EeCceE 20.6 5.9 114.1 6.222362 9.2284e−10 1.00000 N0.180543 0.051636 SxAxxQ ChHhhH 32.9 12.2 229.7 6.116524 1.1926e−091.00000 N 0.143230 0.052898 NxAxxR ChHhhH 18.8 3.4 71.1 8.5756691.4009e−09 1.00000 B 0.264416 0.047686 RxRxxN EeCccC 11.5 1.1 29.610.340734 1.5733e−09 1.00000 B 0.388514 0.035728 LxDxxK CcHhhH 18.8 3.3105.3 8.623619 1.8769e−09 1.00000 B 0.178538 0.031578 GxNxxQ CcChhH 20.64.1 96.7 8.325608 1.9155e−09 1.00000 B 0.213030 0.042410 HxCxxH CcCchH9.8 0.8 14.2 10.365943 2.3489e−09 1.00000 B 0.690141 0.056264 FxHxxHEcHhhH 8.0 0.5 10.3 10.594488 2.7755e−09 1.00000 B 0.776699 0.050930NxFxxA HcCchH 7.3 0.3 12.0 12.967742 2.9756e−09 1.00000 B 0.6083330.024910

TABLE 25 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySxKxDK CeEeEE 56.6 10.6 226.5 14.510498 5.1077e−47 1.00000 N 0.2498900.046621 TxTxKT CcCcHH 27.3 0.4 35.1 41.402645 3.3263e−45 1.00000 B0.777778 0.012151 TxVxKK EeEeEE 68.9 17.0 371.5 12.858963 1.8898e−371.00000 N 0.185464 0.045880 DxAxKT CcCcHH 21.3 0.3 36.1 42.2282241.7463e−36 1.00000 B 0.590028 0.006931 VxCxNG EcCcCC 27.6 1.3 56.322.965619 2.7459e−29 1.00000 B 0.490231 0.023790 SxTxVD HcEeEE 57.7 15.5332.4 10.970812 1.1028e−27 1.00000 N 0.173586 0.046666 DxGxGK CcCcCH23.6 0.8 90.6 25.557645 2.7107e−27 1.00000 B 0.260486 0.008861 GxGxTTCcChHH 38.1 3.9 150.8 17.412946 2.6727e−26 1.00000 B 0.252653 0.026192GxGxST CcChHH 33.8 3.1 132.3 17.712534 5.1241e−25 1.00000 B 0.2554800.023279 SxGxGR CcCcHH 13.2 0.1 48.5 43.386267 6.4655e−25 1.00000 B0.272165 0.001886 SxTxNT CcCcHH 12.5 0.1 11.0 29.834372 8.9716e−221.00000 B 1.136364 0.012207 NxKxDK CeEeEE 29.8 6.4 135.4 9.4820968.5112e−21 1.00000 N 0.220089 0.047229 QxPxSL EeCcEE 27.9 5.8 253.49.267533 6.6594e−20 1.00000 N 0.110103 0.022941 YxSxRT HhCcCC 17.3 0.930.2 18.031141 3.4196e−19 1.00000 B 0.572848 0.028343 CxGxIC EcCcCC 7.00.0 12.0 65.805632 5.1452e−19 1.00000 B 0.583333 0.000941 SxVxKS CcCcHH15.3 0.5 48.4 20.089608 3.7836e−18 1.00000 B 0.316116 0.011271 NxGxTTCcChHH 15.8 0.7 25.1 17.983191 4.6058e−18 1.00000 B 0.629482 0.028833PxWxIG CeEcCC 12.3 0.1 9.3 27.308812 1.0008e−17 1.00000 B 1.3225810.012317 PxHxAL CcHhHC 11.0 0.3 13.1 20.593235 3.3394e−17 1.00000 B0.839695 0.021144 HxAxVA EeEeCC 3.0 0.0 1.0 4.880275 1.0655e−16 1.00000B 3.000000 0.040295 RxTxDD EeEhHH 1.5 0.0 1.0 5.879538 1.0790e−161.00000 B 1.500000 0.028114 DxSxNT CcEhHH 1.0 0.0 1.0 6.0871751.0810e−16 1.00000 B 1.000000 0.026279 LxAxVK ChHhHH 1.0 0.0 1.06.162276 1.0817e−16 1.00000 B 1.000000 0.025658 NxFxDS HhHcCC 1.0 0.01.0 6.660356 1.0857e−16 1.00000 B 1.000000 0.022046 YxIxTG EcCcCC 1.00.0 1.0 7.772472 1.0921e−16 1.00000 B 1.000000 0.016284 MxYxKI CcEeCC1.5 0.0 1.0 8.569222 1.0953e−16 1.00000 B 1.500000 0.013435 GxGxTSCcChHH 13.9 0.6 32.9 18.152055 3.8821e−16 1.00000 B 0.422492 0.016720PxGxGK CcCcCH 19.0 1.4 130.3 14.923143 4.2284e−16 1.00000 B 0.1458170.010785 KxVxCK EeEcCC 17.6 1.4 47.7 14.183369 3.3780e−15 1.00000 B0.368973 0.028318 AxGxGK CcCcCH 13.3 0.5 57.6 17.711953 4.1489e−151.00000 B 0.230903 0.009115 CxAxIG CcCcCC 8.5 0.1 15.5 25.3819032.8396e−14 1.00000 B 0.548387 0.007100 LxNxGK CcCcCH 8.3 0.1 15.024.590088 4.0805e−14 1.00000 B 0.553333 0.007448 SxGxGC EeCcCC 15.3 1.0130.5 14.714935 5.5466e−14 1.00000 B 0.117241 0.007334 NxGxGK CcCcCH 9.00.2 15.0 19.702967 6.8088e−14 1.00000 B 0.600000 0.013474 SxGxGR CcCcCH8.5 0.1 23.1 24.809324 8.9712e−14 1.00000 B 0.367965 0.004970 LxNxCRCcCcCH 5.5 0.0 10.6 51.644952 2.5159e−13 1.00000 B 0.518868 0.001067QxGxCW CcCcHH 7.9 0.1 20.2 25.311731 4.5137e−13 1.00000 B 0.3910890.004729 CxAxVG CcCcCH 6.8 0.0 17.8 31.472647 1.0357e−12 1.00000 B0.382022 0.002594 LxGxGK CcCcCH 12.9 0.7 55.2 14.339566 1.0848e−121.00000 B 0.233696 0.013224 NxTxNR HhChHH 13.8 1.0 47.4 13.0352042.7237e−12 1.00000 B 0.291139 0.020818 MxTxKF HcCcCE 7.5 0.1 11.820.657897 5.9295e−12 1.00000 B 0.635593 0.010909 QxSxKT CcCcHH 7.2 0.117.7 21.756070 6.1332e−12 1.00000 B 0.406780 0.006042 AxRxNF CcCcCE 7.30.1 18.3 21.494990 8.0400e−12 1.00000 B 0.398907 0.006148 QxGxGK CcCcCH11.5 0.6 50.9 14.221165 8.7531e−12 1.00000 B 0.225933 0.011689 TxNxGEEeCcCE 7.5 0.2 7.5 15.735409 2.9385e−11 1.00000 B 1.000000 0.029400IxNxTP EcCcCC 9.6 0.3 51.6 15.771712 3.0578e−11 1.00000 B 0.1860470.006716 CxAxIG CcCcCH 4.8 0.0 9.7 49.375090 3.2308e−11 1.00000 B0.494845 0.000971 TxCxVH CcEeEE 5.3 0.0 7.0 29.062670 3.3981e−11 1.00000B 0.757143 0.004714 YxDxFQ CcCcCC 6.8 0.1 16.8 23.103835 3.7298e−111.00000 B 0.404762 0.005054 AxNxRV CcChHH 8.3 0.1 6.4 18.9087174.2509e−11 1.00000 B 1.296875 0.017585 GxGxSA CcChHH 14.5 1.5 84.510.890707 1.2556e−10 1.00000 B 0.171598 0.017267 AxGxTT CcChHH 9.0 0.422.7 13.379300 1.3988e−10 1.00000 B 0.396476 0.018462 SxGxCW CcEcHH 5.70.0 11.5 27.137424 1.4181e−10 1.00000 B 0.495652 0.003792 RxRxFN EeCcCC7.5 0.1 6.0 15.932390 1.5159e−10 1.00000 B 1.250000 0.023091 QxSxGACcCcEC 5.2 0.1 5.0 21.291482 1.5452e−10 1.00000 B 1.040000 0.010909MxLxTL EeCcCC 7.0 0.2 11.1 15.638597 1.6234e−10 1.00000 B 0.6306310.017371 TxSxKT CcCcHH 10.5 0.6 48.6 12.982231 1.7709e−10 1.00000 B0.216049 0.012137 DxHxIG CcCcHH 6.0 0.1 7.3 17.182429 2.0446e−10 1.00000B 0.821918 0.016313 NxQxQF CcCcCE 10.1 0.6 29.2 11.908196 3.6689e−101.00000 B 0.345890 0.022079 LxVxMV CeEeEE 3.3 0.0 9.0 78.4945934.4384e−10 1.00000 B 0.366667 0.000196 QxQxIM CcCcHH 4.8 0.0 5.031.368999 4.7125e−10 1.00000 B 0.960000 0.004659 RxVxYT EeCcCC 9.1 0.523.1 12.387539 5.4387e−10 1.00000 B 0.393939 0.021353 HxDxGK CcCcCH 8.00.3 38.9 13.707911 9.2865e−10 1.00000 B 0.205656 0.008142 GxGxGR CcChHH8.0 0.4 11.6 11.785433 1.0014e−09 1.00000 B 0.689655 0.036945 WxHxYACcCcHH 5.0 0.0 4.0 24.146704 2.1553e−09 1.00000 B 1.250000 0.006814WxNxFT HhHcCC 5.9 0.1 9.1 18.284331 2.4343e−09 1.00000 B 0.6483520.011176 FxExLT HhHhHH 14.2 1.8 105.3 9.392605 2.8537e−09 1.00000 B0.134853 0.016894 NxFxVA HcCcHH 6.3 0.2 8.0 14.231463 3.2657e−09 1.00000B 0.787500 0.023607 GxTxKT CcCcHH 8.0 0.4 32.0 12.304709 3.7481e−091.00000 B 0.250000 0.012108 GxGxSS CcChHH 10.7 0.9 51.2 10.7273844.1924e−09 1.00000 B 0.208984 0.016726 VxWxRG EeEcCC 4.6 0.0 5.324.562668 5.3187e−09 1.00000 B 0.867925 0.006561 ExGxSK EcCcCE 12.8 1.547.4 9.353019 5.8809e−09 1.00000 B 0.270042 0.031772 SxGxGK CcCcCH 8.60.5 34.6 12.115751 6.1620e−09 1.00000 B 0.248555 0.013228 QxRxYG CcCcHH6.8 0.2 9.1 13.511358 6.4034e−09 1.00000 B 0.747253 0.026595 TxPxVYEcCeEE 8.3 0.4 243.9 12.511059 7.2393e−09 1.00000 B 0.034030 0.001638VxHxKT CcCcHH 6.5 0.2 27.7 15.523646 7.7837e−09 1.00000 B 0.2346570.006044 YxFxLH CcEeEE 4.0 0.0 4.0 20.532673 7.8032e−09 1.00000 B1.000000 0.009399 DxRxTG EeEeCC 13.2 1.7 50.0 8.897809 8.4666e−091.00000 B 0.264000 0.034462 GxVxKS CcCcHH 9.1 0.6 60.0 10.7833661.1852e−08 1.00000 B 0.151667 0.010405 AxTxKS CcCcHH 4.0 0.0 5.521.215041 1.4941e−08 1.00000 B 0.727273 0.006391 GxCxSC CcCcCH 4.6 0.029.3 25.245739 1.5299e−08 1.00000 B 0.156997 0.001118 GxGxSI EcCeEE 5.50.1 7.2 15.694859 1.5981e−08 1.00000 B 0.763889 0.016598 KxYxME CcCcCC8.4 0.5 19.0 10.767521 1.6629e−08 1.00000 B 0.442105 0.028822 ExCxLGEcCcCC 5.0 0.1 5.8 13.975310 1.9806e−08 1.00000 B 0.862069 0.021445DxGxTT CcChHH 9.6 0.8 37.4 10.287614 1.9873e−08 1.00000 B 0.2566840.020174 NxAxKN EeCcCC 13.3 1.9 44.0 8.403028 2.1730e−08 1.00000 B0.302273 0.043597 SxVxKT EeEeEE 11.0 1.3 38.0 8.833970 2.7438e−081.00000 B 0.289474 0.033101 GxGxSC CcChHH 8.5 0.6 21.8 10.4797582.9812e−08 1.00000 B 0.389908 0.026882 RxGxGR CcChHH 7.5 0.4 12.010.790353 3.2673e−08 1.00000 B 0.625000 0.037003 GxTxEK CeEeEE 13.1 2.043.0 8.118745 3.5492e−08 1.00000 B 0.304651 0.045807 GxSxET CcChHH 11.71.4 40.7 8.739976 4.0137e−08 1.00000 B 0.287469 0.035156 GxGxSN CcChHH6.3 0.2 15.3 12.729469 4.2660e−08 1.00000 B 0.411765 0.015085 SxSxKSCcCcHH 7.7 0.4 27.8 11.446286 4.3518e−08 1.00000 B 0.276978 0.014804LxPxEF CcChHH 7.0 0.4 10.5 10.018015 4.4979e−08 1.00000 B 0.6666670.042563 IxGxSA HhCcHH 5.0 0.2 5.0 11.874412 4.7104e−08 1.00000 B1.000000 0.034246 GxDxYR CcCcEC 14.6 2.5 56.5 7.900639 5.0007e−081.00000 B 0.258407 0.043651 QxRxLG CcCcHH 5.0 0.1 8.0 13.8854215.0566e−08 1.00000 B 0.625000 0.015651 VxFxFP CcCcCC 8.6 0.7 16.09.682042 5.1444e−08 1.00000 B 0.537500 0.043541 NxFxGS CcEeEC 5.5 0.25.0 11.627430 5.7697e−08 1.00000 B 1.100000 0.035664

TABLE 26 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityGxGKxT CcCHhH 78.2 4.7 290.1 34.047316 1.1506e−69 1.00000 B 0.2695620.016316 SxKVxK CeEEeE 59.8 11.1 226.5 14.982640 4.7717e−50 1.00000 N0.264018 0.049037 TxTGxT CcCChH 31.0 0.7 40.9 36.555165 1.3620e−461.00000 B 0.757946 0.017091 VxCKxG EcCCcC 37.2 1.7 58.6 27.6467913.2831e−42 1.00000 B 0.634812 0.028979 DxAGxT CcCChH 21.3 0.2 35.945.944381 5.1346e−38 1.00000 B 0.593315 0.005903 TxVDxK EeEEeE 69.3 18.1368.2 12.323075 1.5043e−34 1.00000 N 0.188213 0.049248 NxGKxT CcCHhH23.8 0.7 46.8 27.221369 5.7232e−30 1.00000 B 0.508547 0.015591 GxGKxSCcCHhH 23.6 0.7 72.6 26.546387 2.5060e−28 1.00000 B 0.325069 0.010313SxTKxD HcEEeE 56.0 15.5 313.0 10.555618 9.5006e−26 1.00000 N 0.1789140.049499 FxGHxA CcCHhH 10.6 0.1 13.0 40.140334 2.0626e−21 1.00000 B0.815385 0.005323 CxAGxG CcCCcH 10.3 0.1 39.0 42.746343 2.0803e−201.00000 B 0.264103 0.001474 AxGKxT CcCHhH 14.4 0.3 36.4 25.1270093.3324e−20 1.00000 B 0.395604 0.008706 DxGVxK CcCCcH 15.1 0.4 50.923.714451 3.6388e−20 1.00000 B 0.296660 0.007620 NxKVxK CeEEeE 30.8 6.9138.8 9.289826 4.7236e−20 1.00000 N 0.221902 0.050018 PxWNxG CeECcC 13.50.1 10.5 30.708828 4.8231e−20 1.00000 B 1.285714 0.011012 YxSGxT HhCCcC18.3 0.9 32.0 18.088408 6.9501e−20 1.00000 B 0.571875 0.029635 CxNGxTCcCCcC 19.0 1.2 51.6 16.572407 2.1832e−18 1.00000 B 0.368217 0.022926SxVGxS CcCChH 15.3 0.6 42.3 19.232519 8.8090e−18 1.00000 B 0.3617020.014021 TxDDxQ EhHHhH 1.0 0.0 1.0 5.392626 1.0733e−16 1.00000 B1.000000 0.033244 CxGNxC EcCCcC 7.5 0.0 17.1 48.331529 1.0735e−161.00000 B 0.438596 0.001401 AxKLxP EeCCcC 1.7 0.0 1.0 5.9660171.0799e−16 1.00000 B 1.700000 0.027327 FxISxI HcCCcE 1.8 0.0 1.05.996760 1.0802e−16 1.00000 B 1.800000 0.027055 MxYIxI CcEEcC 1.5 0.01.0 7.242638 1.0895e−16 1.00000 B 1.500000 0.018707 YxKIxA EeCCcC 1.50.0 1.0 7.671739 1.0917e−16 1.00000 B 1.500000 0.016707 SxTGxT CcCChH14.5 0.7 35.5 17.037291 7.8231e−16 1.00000 B 0.408451 0.018915 SxGVxRCcCChH 7.3 0.0 19.1 37.942945 3.5076e−15 1.00000 B 0.382199 0.001922GxGKxA CcCHhH 15.5 0.8 83.3 16.034987 4.2733e−15 1.00000 B 0.1860740.010132 MxLCxL EeCCcC 7.0 0.0 9.1 31.828768 4.5925e−15 1.00000 B0.769231 0.005270 GxGFxI EcCEeE 8.2 0.1 10.9 24.137133 1.5684e−141.00000 B 0.752294 0.010406 PxGSxK CcCCcH 11.0 0.4 37.7 17.9740374.3376e−14 1.00000 B 0.291777 0.009394 VxWGxG EeECcC 15.8 1.1 116.614.134376 1.1466e−13 1.00000 B 0.135506 0.009373 SxGIxR CcCChH 5.9 0.020.2 52.593321 1.5200e−13 1.00000 B 0.292079 0.000621 MxTFxF HcCCcE 7.50.1 10.7 26.233866 1.6674e−13 1.00000 B 0.700935 0.007532 LxNAxK CcCCcH6.3 0.0 10.5 34.674409 2.0201e−13 1.00000 B 0.600000 0.003121 QxRGxGCcCChH 11.8 0.6 17.1 14.463365 3.4044e−13 1.00000 B 0.690058 0.036257SxGIxR CcCCcH 7.5 0.1 16.7 25.614984 6.6714e−13 1.00000 B 0.4491020.005044 NxACxN EeCCcC 14.3 1.1 43.0 12.984350 9.3387e−13 1.00000 B0.332558 0.024775 NxTPxL CcCCcC 11.8 0.6 39.8 14.917012 1.9147e−121.00000 B 0.296482 0.014437 NxTPxR HhCHhH 13.9 1.0 46.4 12.9093022.3592e−12 1.00000 B 0.299569 0.021942 DxDGxG CcCCcC 35.9 11.9 416.77.054973 2.4585e−12 1.00000 N 0.086153 0.028573 DxGTxK CcCCcH 8.0 0.231.0 18.449093 9.3255e−12 1.00000 B 0.258065 0.005829 SxGAxW CcEChH 5.20.0 5.0 26.461826 1.7914e−11 1.00000 B 1.040000 0.007090 SxYQxE ChHHhH14.9 1.6 34.9 10.894015 1.9565e−11 1.00000 B 0.426934 0.044931 KxYRxECcCCcC 11.8 0.8 21.3 12.330460 1.9943e−11 1.00000 B 0.553991 0.038696QxKGxG CcCChH 10.0 0.6 14.0 12.292249 2.1041e−11 1.00000 B 0.7142860.043579 GxSIxG CeEEeE 9.5 0.3 35.1 15.756244 2.2978e−11 1.00000 B0.270655 0.009721 AxGVxK CcCCcH 7.6 0.1 32.6 20.714517 2.3926e−111.00000 B 0.233129 0.004005 QxGTxK CcCCcH 7.5 0.1 16.6 19.2979993.0906e−11 1.00000 B 0.451807 0.008825 GxGIxS CcCHhH 9.9 0.4 25.914.435885 3.2374e−11 1.00000 B 0.382239 0.016875 FxVAxN CcHHhH 7.8 0.210.5 17.204917 3.4705e−11 1.00000 B 0.742857 0.018948 SxKPxY CcCCcC 12.31.0 23.8 11.403495 4.1050e−11 1.00000 B 0.516807 0.042941 SxSGxS CcCChH7.7 0.2 22.4 18.639391 6.4291e−11 1.00000 B 0.343750 0.007350 CxAGxGCcCCcC 8.3 0.3 28.1 16.106786 8.0611e−11 1.00000 B 0.295374 0.008965QxSGxT CcCChH 7.2 0.2 19.1 17.864972 9.7007e−11 1.00000 B 0.3769630.008205 GxGKxF CcCHhH 9.0 0.4 20.6 12.995440 1.8542e−10 1.00000 B0.436893 0.021509 LxGAxK CcCCcH 6.5 0.1 16.9 20.766526 1.8659e−101.00000 B 0.384615 0.005660 KxQSxQ HhCCcC 5.2 0.0 7.1 23.5001582.7200e−10 1.00000 B 0.732394 0.006815 DxPExL EhHHhH 12.7 1.2 38.010.917952 2.7228e−10 1.00000 B 0.334211 0.030355 GxCGxC CcCCcH 7.4 0.231.3 17.167182 2.9306e−10 1.00000 B 0.236422 0.005687 VxHGxT CcCChH 6.50.1 27.3 20.643805 2.9544e−10 1.00000 B 0.238095 0.003537 GxGKxN CcCHhH6.3 0.1 19.0 19.922337 3.2745e−10 1.00000 B 0.331579 0.005128 NxGRxVChHHhH 7.3 0.2 22.1 16.537083 3.4130e−10 1.00000 B 0.330317 0.008444FxTMxR ChHHhH 9.5 0.5 17.4 12.380879 3.5175e−10 1.00000 B 0.5459770.031061 KxVAxK EeECcC 15.3 2.0 42.0 9.504713 4.1563e−10 1.00000 B0.364286 0.048679 LxNIxR CcCCcH 4.0 0.0 7.8 34.838623 4.8974e−10 1.00000B 0.512821 0.001682 DxRExG EeEEcC 14.2 1.7 48.0 9.784977 5.8536e−101.00000 B 0.295833 0.035279 DxQAxC HhHHhH 12.0 1.1 49.1 10.4146598.3369e−10 1.00000 B 0.244399 0.022756 NxGSxK CcCCcH 4.0 0.0 4.628.935098 8.3475e−10 1.00000 B 0.869565 0.004132 RxVNxT EeCCcC 9.1 0.526.4 12.189591 8.6890e-10 1.00000 B 0.344697 0.019193 NxRGxS CeCCeC 15.22.1 44.0 9.190897 9.0030e−10 1.00000 B 0.345455 0.048322 RxQGxG CcCChH7.7 0.3 8.6 12.844513 9.3322e−10 1.00000 B 0.895349 0.039740 QxQGxGCcCChH 7.0 0.3 9.8 13.041557 1.1860e−09 1.00000 B 0.714286 0.027924DxGKxT CcCHhH 10.5 0.7 46.5 11.532441 1.2908e−09 1.00000 B 0.2258060.015683 GxTGxT CcCChH 8.2 0.3 36.7 13.463242 1.3489e−09 1.00000 B0.223433 0.009366 NxGKxS CcCHhH 8.0 0.4 16.1 12.288612 1.4453e−091.00000 B 0.496894 0.024397 IxGSxK CcCCcH 4.0 0.0 6.0 28.7178321.5897e−09 1.00000 B 0.666667 0.003213 PxSLxV CcEEeE 19.5 3.5 165.58.628967 1.9034e−09 1.00000 B 0.117825 0.021201 SxVExT EeEEeE 12.4 1.430.8 9.647297 2.1655e−09 1.00000 B 0.402597 0.044428 GxGYxT CcCHhH 7.50.3 11.7 13.194752 2.3128e−09 1.00000 B 0.641026 0.026093 TxCGxH CcEEeE5.3 0.0 4.0 23.792462 2.4238e−09 1.00000 B 1.325000 0.007017 RxRPxNEeCCcC 8.5 0.5 19.0 12.095644 3.2320e−09 1.00000 B 0.447368 0.023862VxGYxT CcCHhH 6.0 0.2 6.1 12.352805 3.3436e−09 1.00000 B 0.9836070.037190 RxTGxS EeCCcC 12.3 1.3 50.0 9.683731 3.9672e−09 1.00000 B0.246000 0.026408 GxGKxC CcCHhH 8.5 0.5 23.7 12.085767 4.5202e−091.00000 B 0.358650 0.019074 KxKAxH HcCCcC 5.0 0.1 5.0 14.6659406.0513e−09 1.00000 B 1.000000 0.022718 DxHDxG CcCChH 6.0 0.2 10.813.860542 7.7869e−09 1.00000 B 0.555556 0.016605 QxGSxW CcCChH 6.1 0.224.7 15.059254 8.6876e−09 1.00000 B 0.246964 0.006346 CxGGxM HhCCcH 8.00.4 26.4 11.415826 8.9656e−09 1.00000 B 0.303030 0.016873 NxFCxS CcEEeC5.5 0.1 5.0 13.483966 1.3733e−08 1.00000 B 1.100000 0.026764 KxSQxKEeCCcC 6.0 0.0 4.0 18.700567 1.6355e−08 1.00000 B 1.500000 0.011309TxNIxE EeCCcE 6.3 0.3 6.3 11.104803 1.7890e−08 1.00000 B 1.0000000.048605 NxFTxA HcCChH 6.3 0.2 8.6 12.485050 1.8314e−08 1.00000 B0.732558 0.028168 ExGGxW CcCCcE 6.5 0.2 13.3 13.527432 1.8754e−081.00000 B 0.488722 0.016480 TxAQxE ChHHhH 10.1 1.0 32.5 9.4038152.1503e−08 1.00000 B 0.310769 0.029888 TxVFxN EeEEcC 5.4 0.1 11.216.298617 2.3107e−08 1.00000 B 0.482143 0.009509 RxDTxQ HhCCcC 5.5 0.15.2 13.252766 2.4042e−08 1.00000 B 1.057692 0.028755 DxEGxP HhHCcC 15.12.6 55.1 7.886866 2.6898e−08 1.00000 B 0.274047 0.047668 GxGFxL EcCEeE4.3 0.0 5.9 20.203205 3.1103e−08 1.00000 B 0.728814 0.007577 FxYSxDCcCCcC 5.9 0.2 8.0 13.568243 3.5331e−08 1.00000 B 0.737500 0.022718

TABLE 27 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySxKVDK CeEEEE 55.6 9.0 226.6 15.848462 1.0626e−55 1.00000 N 0.2453660.039728 TxVDKK EeEEEE 68.9 14.4 363.1 14.631509 6.3100e−48 1.00000 N0.189755 0.039746 TxTGKT CcCCHH 27.3 0.4 34.1 41.712557 1.1510e−451.00000 B 0.800587 0.012329 DxAGKT CcCCHH 21.3 0.1 35.9 67.1489077.5094e−45 1.00000 B 0.593315 0.002784 GxGKTT CcCHHH 37.1 1.7 139.727.458764 2.4284e−38 1.00000 B 0.265569 0.012053 SxTKVD HcEEEE 55.5 12.5313.0 12.416336 6.4044e−35 1.00000 N 0.177316 0.039921 GxGKST CcCHHH30.9 1.2 106.0 27.358680 4.2728e−34 1.00000 B 0.291509 0.011250 VxCKNGEcCCCC 26.6 1.4 55.2 21.380843 4.0094e−27 1.00000 B 0.481884 0.025784NxKVDK CeEEEE 29.8 5.5 135.3 10.625194 1.1533e−25 1.00000 N 0.2202510.040399 NxGKTT CcCHHH 15.8 0.3 24.1 29.281293 3.1531e−24 1.00000 B0.655602 0.011790 DxGVGK CcCCCH 15.1 0.2 50.6 32.811283 3.2521e−241.00000 B 0.298419 0.004088 SxTGNT CcCCHH 12.5 0.1 11.0 29.9878508.0249e−22 1.00000 B 1.136364 0.012084 SxVGKS CcCCHH 15.3 0.3 41.726.658271 8.7346e−22 1.00000 B 0.366906 0.007632 CxGNIC EcCCCC 7.0 0.012.0 95.810125 2.7036e−21 1.00000 B 0.583333 0.000444 GxGKTS CcCHHH 13.90.2 31.5 28.626452 4.2468e−21 1.00000 B 0.441270 0.007293 SxGIGR CcCCCH7.5 0.0 14.7 93.158277 8.5854e−21 1.00000 B 0.510204 0.000440 YxSGRTHhCCCC 17.3 0.7 30.2 19.573147 2.6454e−20 1.00000 B 0.572848 0.024310SxGVGR CcCCHH 7.3 0.0 18.1 67.069455 1.1733e−18 1.00000 B 0.4033150.000653 PxWNIG CeECCC 12.3 0.1 9.3 27.472358 9.0000e−18 1.00000 B1.322581 0.012172 GxDVVG CcCHHH 2.0 0.0 2.0 8.888636 1.0693e−17 1.00000B 1.000000 0.024689 GxGKSA CcCHHH 14.5 0.5 50.8 20.582995 1.4756e−171.00000 B 0.285433 0.009233 PxGSGK CcCCCH 11.0 0.2 35.4 25.5721582.5256e−17 1.00000 B 0.310734 0.005083 CxAGIG CcCCCC 6.3 0.0 11.974.862067 2.6570e−17 1.00000 B 0.529412 0.000594 HxASVA EeEECC 3.0 0.01.0 5.165831 1.0701e−16 1.00000 B 3.000000 0.036120 AxKGLV HhHCCC 1.00.0 1.0 6.244247 1.0825e−16 1.00000 B 1.000000 0.025006 YxKIHA EeCCCC1.5 0.0 1.0 7.610023 1.0914e−16 1.00000 B 1.500000 0.016974 RxTTLDEeEEEE 1.0 0.0 1.0 7.954816 1.0930e−16 1.00000 B 1.000000 0.015557MxYIKI CcEECC 1.5 0.0 1.0 8.335733 1.0945e−16 1.00000 B 1.5000000.014188 LxARVK ChHHHH 1.0 0.0 1.0 8.511831 1.0951e−16 1.00000 B1.000000 0.013614 RxLFLE CcCHHH 1.0 0.0 1.0 9.594150 1.0983e−16 1.00000B 1.000000 0.010747 GxRDNG CcEEEE 1.0 0.0 1.0 10.319729 1.0999e−161.00000 B 1.000000 0.009303 LxNAGK CcCCCH 6.3 0.0 10.5 61.3217302.2405e−16 1.00000 B 0.600000 0.001003 DxGTGK CcCCCH 8.0 0.1 29.035.088156 4.0490e−16 1.00000 B 0.275862 0.001773 SxGIGR CcCCHH 5.9 0.020.2 84.110847 1.3990e−15 1.00000 B 0.292079 0.000243 AxGKTT CcCHHH 9.00.1 21.6 23.820242 7.2402e−15 1.00000 B 0.416667 0.006448 MxLCTL EeCCCC7.0 0.1 9.1 26.549827 5.6450e−14 1.00000 B 0.769231 0.007547 KxVACKEeECCC 15.3 1.2 42.0 13.180952 1.8560e−13 1.00000 B 0.364286 0.028111QxSGKT CcCCHH 7.2 0.1 17.0 26.686569 3.5476e−13 1.00000 B 0.4235290.004215 QxGSCW CcCCHH 6.1 0.0 20.2 34.553496 4.6995e−13 1.00000 B0.301980 0.001530 SxSGKS CcCCHH 7.7 0.1 21.4 26.468945 5.2665e−131.00000 B 0.359813 0.003885 MxTFKF HcCCCE 7.5 0.1 10.7 24.0278085.5753e−13 1.00000 B 0.700935 0.008955 GxTGKT CcCCHH 8.0 0.1 30.922.029457 6.1861e−13 1.00000 B 0.258900 0.004149 GxGIMS CcCHHH 5.0 0.05.0 36.561607 7.1860e−13 1.00000 B 1.000000 0.003726 NxTPNR HhCHHH 13.81.0 46.4 13.288369 1.7188e−12 1.00000 B 0.297414 0.020563 VxHGKT CcCCHH6.5 0.0 27.3 30.546954 3.0058e−12 1.00000 B 0.238095 0.001638 CxAGVGCcCCCH 5.8 0.0 17.8 40.693813 3.0166e−12 1.00000 B 0.325843 0.001135AxGVGK CcCCCH 7.6 0.1 31.0 23.748136 3.6395e−12 1.00000 B 0.2451610.003228 SxGACW CcECHH 5.2 0.0 4.0 53.110192 4.0212e−12 1.00000 B1.300000 0.001416 AxNGDS CcCCCC 5.0 0.0 6.0 33.087901 4.6504e−12 1.00000B 0.833333 0.003786 DxGKTT CcCHHH 9.5 0.3 35.5 17.343265 4.7098e−121.00000 B 0.267606 0.008017 LxNICR CcCCCH 4.0 0.0 7.8 61.8297195.0603e−12 1.00000 B 0.512821 0.000536 CxAGIG CcCCCH 4.5 0.0 9.764.816014 5.4850e−12 1.00000 B 0.463918 0.000496 GxGKSS CcCHHH 9.7 0.334.0 16.497208 9.1680e−12 1.00000 B 0.285294 0.009588 IxNYTP EcCCCC 9.60.3 47.0 16.379090 1.5314e−11 1.00000 B 0.204255 0.006873 NxACKN EeCCCC13.3 1.1 43.0 11.980088 1.8020e−11 1.00000 B 0.309302 0.024858 NxGSGKCcCCCH 4.0 0.0 4.0 42.938701 2.1963e−11 1.00000 B 1.000000 0.002165QxGTGK CcCCCH 7.5 0.1 16.1 19.678453 2.2578e−11 1.00000 B 0.4658390.008763 LxVGMV CeEEEE 3.3 0.0 7.0 117.793861 3.4484e−11 1.00000 B0.471429 0.000112 YxDNFQ CcCCCC 6.8 0.1 15.8 22.244783 5.4167e−111.00000 B 0.430380 0.005790 TxCGVH CcEEEE 5.3 0.0 4.0 36.2675368.4493e−11 1.00000 B 1.325000 0.003032 GxGKSN CcCHHH 6.3 0.1 13.021.117590 1.0495e−10 1.00000 B 0.484615 0.006703 DxHDIG CcCCHH 6.0 0.16.8 17.457699 1.1976e−10 1.00000 B 0.882353 0.016997 RxRPFN EeCCCC 7.50.1 6.0 16.071908 1.3686e−10 1.00000 B 1.250000 0.022701 NxSGKS CcCCHH5.0 0.0 13.1 25.781208 2.4284e−10 1.00000 B 0.381679 0.002837 GxGKSCCcCHHH 8.5 0.3 19.8 14.494190 2.4906e−10 1.00000 B 0.429293 0.016339LxGAGK CcCCCH 6.5 0.1 15.9 19.909508 2.8421e−10 1.00000 B 0.4088050.006534 TxSGKT CcCCHH 10.5 0.6 48.6 12.584345 3.0343e−10 1.00000 B0.216049 0.012838 RxVNYT EeCCCC 9.1 0.5 22.1 12.656039 3.5603e−101.00000 B 0.411765 0.021478 GxVGKS CcCCHH 9.1 0.4 55.2 13.4365933.7410e−10 1.00000 B 0.164855 0.007617 TxNIGE EeCCCE 6.3 0.2 6.314.647106 7.3598e−10 1.00000 B 1.000000 0.028528 PxVGKS CcCCHH 7.5 0.226.5 15.812094 7.6266e−10 1.00000 B 0.283019 0.008077 KxYRME CcCCCC 7.40.2 16.0 15.025400 8.0890e−10 1.00000 B 0.462500 0.014437 GxGLGR CcCHHH7.0 0.1 5.0 17.703901 9.5454e−10 1.00000 B 1.400000 0.015702 QxQGIMCcCCHH 4.8 0.0 5.0 28.122826 1.1237e−09 1.00000 B 0.960000 0.005790KxQSPQ HhCCCC 5.2 0.1 7.1 20.111796 1.2579e−09 1.00000 B 0.7323940.009265 QxRGYG CcCCHH 6.8 0.2 9.1 15.336532 1.4944e−09 1.00000 B0.747253 0.020849 NxGKST CcCHHH 8.0 0.4 22.7 12.520330 2.0100e−091.00000 B 0.352423 0.016606 GxGKTF CcCHHH 8.0 0.4 17.8 12.1103342.1948e−09 1.00000 B 0.449438 0.022622 SxVGKT CcCCHH 6.0 0.1 21.016.640878 2.2754e−09 1.00000 B 0.285714 0.005970 NxFCGS CcEEEC 5.5 0.15.0 15.478503 3.5703e−09 1.00000 B 1.100000 0.020443 NxFTVA HcCCHH 6.30.2 8.1 14.131219 3.6966e−09 1.00000 B 0.777778 0.023628 GxTVEK CeEEEE13.1 1.6 41.1 9.138482 3.7062e−09 1.00000 B 0.318735 0.039863 WxHGYACcCCHH 5.0 0.0 4.0 22.521458 3.7482e−09 1.00000 B 1.250000 0.007824KxKACH HcCCCC 5.0 0.1 5.0 14.885519 5.2330e−09 1.00000 B 1.0000000.022067 KxSQQK EeCCCC 6.0 0.0 4.0 20.959247 6.6296e−09 1.00000 B1.500000 0.009023 ExTFPD CcCCCC 8.6 0.6 14.0 10.957842 6.6646e−091.00000 B 0.614286 0.040051 VxFTFP CcCCCC 8.6 0.6 14.0 10.9482376.7483e−09 1.00000 B 0.614286 0.040115 VxWGRG EeECCC 4.6 0.0 5.323.040320 8.8272e−09 1.00000 B 0.867925 0.007448 GxGYAT CcCHHH 5.0 0.04.0 20.181971 8.9445e−09 1.00000 B 1.250000 0.009725 IxGSGK CcCCCH 4.00.0 6.0 22.389604 1.1417e−08 1.00000 B 0.666667 0.005264 DxRETG EeEECC12.2 1.5 48.0 8.975496 1.4213e−08 1.00000 B 0.254167 0.030697 GxGKGTCcCHHH 10.2 1.0 37.7 9.601553 1.9441e−08 1.00000 B 0.270557 0.025246SxGAGK CcCCCH 4.6 0.0 7.0 21.675509 2.2554e−08 1.00000 B 0.6571430.006351 VxGYGT CcCHHH 5.8 0.2 6.1 13.788700 2.4146e−08 1.00000 B0.950820 0.028106 SxKPLY CcCCCC 8.6 0.7 16.0 10.023813 3.1924e−081.00000 B 0.537500 0.040940 HxDHGK CcCCCH 5.0 0.1 33.0 16.4576633.2287e−08 1.00000 B 0.151515 0.002705 QxRGLG CcCCHH 5.0 0.1 7.014.024044 3.4288e−08 1.00000 B 0.714286 0.017585 GxGFSI EcCEEE 4.0 0.14.4 17.653767 3.6548e−08 1.00000 B 0.909091 0.011507 IxGNSA HhCCHH 5.00.2 5.0 12.190063 3.6553e−08 1.00000 B 1.000000 0.032553

TABLE 28 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilityGLxxxQ CCchhH 54.6 10.0 239.5 14.376318 3.6957e−46 1.00000 N 0.2279750.041884 EVxxxW CCchhH 23.1 0.5 25.5 31.732726 8.9916e−37 1.00000 B0.905882 0.020272 GIxxxQ CCchhH 44.1 8.5 170.0 12.547464 1.8680e−351.00000 N 0.259412 0.049891 STxxxK CEeeeE 68.0 18.7 273.9 11.8054457.5425e−32 1.00000 N 0.248266 0.068310 LSxxxH HHhhhH 34.7 6.5 227.611.162649 2.8341e−28 1.00000 N 0.152460 0.028772 GSxxxT CCchhH 36.4 3.6141.4 17.566235 8.1592e−26 1.00000 B 0.257426 0.025327 NPxxxE CCchhH30.1 5.6 135.5 10.539187 2.7481e−25 1.00000 N 0.222140 0.041521 GLxxxECCchhH 55.6 15.7 370.9 10.286605 1.5314e−24 1.00000 N 0.149906 0.042345TQxxxT CCcchH 18.0 0.7 24.5 21.679320 1.1385e−23 1.00000 B 0.7346940.026840 GFxxxD CCchhH 35.3 7.7 175.1 10.141682 1.1664e−23 1.00000 N0.201599 0.044152 GGxxxN CCchhH 27.3 5.1 106.7 10.105386 2.5924e−231.00000 N 0.255858 0.047587 CSxxxG CCcccH 11.6 0.1 36.9 42.9381115.1216e−22 1.00000 B 0.314363 0.001957 VAxxxG ECcccC 36.9 5.0 129.314.592371 8.2210e−22 1.00000 B 0.285383 0.038494 LPxxxR CChhhH 31.2 6.7201.9 9.644138 1.7359e−21 1.00000 N 0.154532 0.033103 SLxxxE CCchhH 36.69.3 220.9 9.134791 1.5180e−19 1.00000 N 0.165686 0.042167 GVxxxE CCchhH38.3 10.2 238.7 8.992735 5.1079e−19 1.00000 N 0.160452 0.042731 KExxxACCchhH 25.3 5.2 85.5 9.049696 5.5135e−19 1.00000 N 0.295906 0.061241CKxxxT CCcccC 29.6 3.7 96.1 13.675704 1.2906e−18 1.00000 B 0.3080120.038755 LSxxxQ CChhhH 25.1 5.2 186.8 8.904430 1.9586e−18 1.00000 N0.134368 0.027613 TGxxxT CCcchH 26.5 5.8 112.2 8.834358 3.3175e−181.00000 N 0.236185 0.051631 LSxxxR CChhhH 40.4 11.5 293.2 8.6620638.5519e−18 1.00000 N 0.137790 0.039389 DLxxxE CCchhH 30.3 7.4 187.58.615766 1.7599e−17 1.00000 N 0.161600 0.039316 FSxxxY HHcccH 1.1 0.11.0 4.074728 1.0472e−16 1.00000 B 1.100000 0.056807 NMxxxE CCchhH 27.03.8 79.7 12.253842 1.9659e−16 1.00000 B 0.338770 0.047324 LTxxxR CChhhH30.4 7.8 203.9 8.238198 3.9476e−16 1.00000 N 0.149093 0.038329 YAxxxTHHcccC 20.8 2.0 55.2 13.691929 4.2721e−16 1.00000 B 0.376812 0.035555LTxxxK CChhhH 29.4 7.5 198.1 8.183120 6.3961e−16 1.00000 N 0.1484100.037688 QSxxxL EEcceE 30.2 7.8 260.2 8.169296 6.9027e−16 1.00000 N0.116065 0.029863 ERxxxD HHhheC 16.2 1.0 36.2 15.054070 8.6591e−161.00000 B 0.447514 0.028832 LDxxxR CChhhH 32.5 8.9 240.5 8.0688691.4172e−15 1.00000 N 0.135135 0.036966 TKxxxC CChhhH 11.0 0.5 12.014.531388 1.8514e−14 1.00000 B 0.916667 0.045202 CExxxY EEcccC 17.7 1.550.9 13.362872 2.0202e−14 1.00000 B 0.347741 0.029713 SWxxxC EEcccC 15.50.9 140.2 15.144607 2.9263e−14 1.00000 B 0.110556 0.006644 SAxxxR CHhhhH38.1 12.2 224.6 7.644138 3.2710e−14 1.00000 N 0.169635 0.054175 VQxxxSECcccC 25.7 6.6 164.8 7.619327 5.8468e−14 1.00000 N 0.155947 0.039850NLxxxD CCchhH 24.9 6.2 242.5 7.619062 6.0600e−14 1.00000 N 0.1026800.025522 ELxxxE CCchhH 27.3 7.3 172.9 7.544366 9.5073e−14 1.00000 N0.157895 0.042349 GVxxxA CCchhH 27.9 4.8 176.5 10.653267 1.3946e−131.00000 B 0.158074 0.027331 YHxxxE HHhhhH 23.2 5.7 128.6 7.5160351.4229e−13 1.00000 N 0.180404 0.044191 TVxxxE CHhhhH 24.2 6.2 110.17.404460 3.0474e−13 1.00000 N 0.219800 0.056658 SAxxxR CCcchH 16.6 1.468.1 12.837428 3.2464e−13 1.00000 B 0.243759 0.020953 PTxxxG CEeccC 16.51.4 85.8 12.894317 4.0322e−13 1.00000 B 0.192308 0.016258 QTxxxK CCcccH14.2 1.0 50.3 13.307139 6.6972e−13 1.00000 B 0.282306 0.019950 TKxxxKEEeeeE 67.0 29.5 480.9 7.130159 9.9543e−13 1.00000 N 0.139322 0.061317GAxxxT CCchhH 26.4 4.7 165.8 10.161537 1.2729e−12 1.00000 B 0.1592280.028319 LSxxxK CChhhH 29.4 8.7 241.0 7.163028 1.3727e−12 1.00000 N0.121992 0.036016 GYxxxN CEchhH 14.0 1.1 42.3 12.536419 1.6774e−121.00000 B 0.330969 0.025738 NTxxxK CEeeeE 33.8 11.0 168.6 7.1166821.6931e−12 1.00000 N 0.200474 0.065182 DNxxxP CChhhH 5.3 0.0 5.032.897939 2.0566e−12 1.00000 B 1.060000 0.004599 WLxxxH HHcccC 15.4 1.451.8 12.142070 2.2839e−12 1.00000 B 0.297297 0.026471 RAxxxR HHhhhH 62.927.3 536.8 6.997202 2.6193e−12 1.00000 N 0.117176 0.050836 EAxxxE HHhhhH84.2 40.9 815.1 6.937320 3.5127e−12 1.00000 N 0.103300 0.050228 GLxxxIECceeE 9.7 0.4 17.7 15.497102 8.0689e−12 1.00000 B 0.548023 0.020915ACxxxS CCcccC 19.1 2.5 123.5 10.614314 8.2065e−12 1.00000 B 0.1546560.020220 GVxxxD CCchhH 23.4 6.3 189.3 6.927950 8.7577e−12 1.00000 N0.123613 0.033287 LSxxxI CChhhH 25.4 7.1 404.3 6.907684 9.1681e−121.00000 N 0.062825 0.017623 QTxxxK HHhhhH 25.6 7.4 144.0 6.8322541.5255e−11 1.00000 N 0.177778 0.051705 SSxxxD HCeeeE 41.2 15.6 216.66.724105 2.1591e−11 1.00000 N 0.190212 0.072065 GVxxxQ CCehhH 10.9 0.69.5 11.942747 2.4637e−11 1.00000 B 1.147368 0.062447 NAxxxQ HHhhhH 20.65.3 129.5 6.788754 2.5681e−11 1.00000 N 0.159073 0.040908 CHxxxR HHhhhC11.0 0.9 14.0 10.896171 2.8578e−11 1.00000 B 0.785714 0.065457 GVxxxSCCchhH 21.8 3.7 118.3 9.593989 3.8268e−11 1.00000 B 0.184277 0.031117GRxxxE CCchhH 25.7 7.7 147.8 6.680390 4.1501e−11 1.00000 N 0.1738840.051943 PGxxxL CChhhC 18.3 2.5 95.4 10.049115 5.2259e−11 1.00000 B0.191824 0.026518 SAxxxK CHhhhH 30.0 9.9 163.6 6.620898 5.3547e−111.00000 N 0.183374 0.060226 AAxxxT CCchhH 14.1 1.4 47.8 10.7515727.3154e−11 1.00000 B 0.294979 0.029943 FPxxxT HHhhhH 22.4 4.2 81.39.076903 7.4347e−11 1.00000 B 0.275523 0.052004 RExxxR HHhhhH 94.3 50.1805.4 6.456703 8.6412e−11 1.00000 N 0.117085 0.062155 HLxxxH CCcchH 10.00.6 18.2 12.034072 9.4334e−11 1.00000 B 0.549451 0.034515 EFxxxD EEchhH6.7 0.1 18.7 21.811739 1.0142e−10 1.00000 B 0.358289 0.004932 SGxxxDEEeccE 50.1 21.4 292.4 6.445800 1.1982e−10 1.00000 N 0.171341 0.073174FTxxxN CChhhH 10.0 0.6 19.8 12.030980 1.2267e−10 1.00000 B 0.5050510.031658 RIxxxQ CCchhH 14.1 1.5 60.7 10.622272 1.3315e−10 1.00000 B0.232290 0.023928 QCxxxH HHhhhH 13.0 1.3 29.3 10.304706 1.5452e−101.00000 B 0.443686 0.045783 GFxxxG CEeeeE 11.7 0.8 72.6 12.1206112.1618e−10 1.00000 B 0.161157 0.011234 CLxxxC ECcccC 6.5 0.1 11.019.364662 2.2273e−10 1.00000 B 0.590909 0.009999 TCxxxH HHhhhH 10.8 0.727.1 11.927434 2.8064e−10 1.00000 B 0.398524 0.027021 TAxxxE CHhhhH 29.19.8 179.3 6.350328 3.0867e−10 1.00000 N 0.162298 0.054574 PTxxxL CChhhH23.0 6.7 322.9 6.377182 3.1697e−10 1.00000 N 0.071229 0.020700 LDxxxKECcccH 8.5 0.4 15.3 13.692060 3.4070e−10 1.00000 B 0.555556 0.023649AExxxV HHhhcC 21.2 3.9 171.0 8.898036 3.9391e−10 1.00000 B 0.1239770.022677 KCxxxH HCcccC 10.6 0.8 22.5 11.558959 4.2767e−10 1.00000 B0.471111 0.033381 LHxxxL HHhhcC 15.1 2.0 43.7 9.474868 4.3344e−101.00000 B 0.345538 0.045826 EAxxxQ HHhhhH 45.2 18.8 422.8 6.2372664.7014e−10 1.00000 N 0.106906 0.044414 SPxxxS ECceeE 38.1 14.9 211.26.241420 5.0762e−10 1.00000 N 0.180398 0.070475 TPxxxK CHhhhH 42.6 17.4322.0 6.202797 6.0232e−10 1.00000 N 0.132298 0.054102 GAxxxE CCchhH 24.17.5 181.1 6.195949 9.3108e−10 1.00000 N 0.133076 0.041378 SGxxxS CCcchH29.0 10.1 190.4 6.139692 1.1318e−09 1.00000 N 0.152311 0.052802 EGxxxECCchhH 22.3 6.7 113.1 6.173709 1.1489e−09 1.00000 N 0.197171 0.059666GIxxxE CCchhH 25.4 8.2 190.6 6.143827 1.2211e−09 1.00000 N 0.1332630.042994 GQxxxK CCchhH 15.4 2.3 38.6 8.950992 1.3046e−09 1.00000 B0.398964 0.059134 DSxxxR HHhhhH 25.5 8.4 161.5 6.050940 2.1286e−091.00000 N 0.157895 0.052091 FPxxxA CCchhH 15.2 2.1 79.8 9.1353922.2216e−09 1.00000 B 0.190476 0.026431 GExxxQ CCchhH 16.3 2.6 51.08.660100 2.2929e−09 1.00000 B 0.319608 0.051527 TQxxxS EEeccE 26.8 9.1251.1 6.004098 2.6913e−09 1.00000 N 0.106730 0.036075 SAxxxR CCcccH 11.71.1 36.6 10.133488 2.8456e−09 1.00000 B 0.319672 0.030705 DKxxxP HHhccC19.5 5.7 86.1 6.017973 3.3049e−09 1.00000 N 0.226481 0.065745 KLxxxECCchhH 27.3 9.4 234.8 5.963685 3.3721e−09 1.00000 N 0.116269 0.040002GIxxxT CCchhH 22.5 5.0 143.4 7.993685 3.5299e−09 1.00000 B 0.1569040.034712

TABLE 29 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySTxxDK CEeeEE 59.1 14.2 254.5 12.233583 5.4622e−34 1.00000 N 0.2322200.055962 SAxxGR CCccHH 15.6 0.1 46.1 49.079185 2.2129e−29 1.00000 B0.338395 0.002168 TKxxKK EEeeEE 66.1 19.3 341.6 10.992116 7.5992e−281.00000 N 0.193501 0.056354 TQxxKT CCccHH 15.3 0.2 14.3 29.3397241.6806e−25 1.00000 B 1.069930 0.016341 ERxxMD HHhhEC 15.1 0.2 36.230.598992 8.7736e−24 1.00000 B 0.417127 0.006560 PTxxIG CEecCC 14.3 0.212.4 30.481402 5.0639e−23 1.00000 B 1.153226 0.013170 SAxxGR CCccCH 11.70.1 21.6 43.188076 9.9068e−23 1.00000 B 0.541667 0.003367 LSxxYH HHhhHH26.5 2.5 52.5 15.583360 4.0718e−21 1.00000 B 0.504762 0.047463 GSxxSTCCchHH 17.9 0.8 49.1 19.913960 7.6094e−20 1.00000 B 0.364562 0.015335YAxxRT HHccCC 18.3 1.0 30.1 17.537770 1.2259e−19 1.00000 B 0.6079730.033422 CSxxIG CCccCC 8.5 0.0 12.3 52.662194 1.3010e−19 1.00000 B0.691057 0.002110 TGxxKT CCccHH 24.5 2.2 85.8 15.179670 9.8763e−191.00000 B 0.285548 0.025790 TExxSI HHhcCC 3.0 0.1 2.0 7.7704431.3782e−17 1.00000 B 1.500000 0.032062 CSxxVG CCccCH 6.8 0.0 16.077.222504 2.0499e−17 1.00000 B 0.425000 0.000484 QSxxSL EEccEE 25.0 5.4183.2 8.519344 5.1349e−17 1.00000 N 0.136463 0.029668 NAxxQV CCchHH 1.00.0 1.0 4.478223 1.0575e−16 1.00000 B 1.000000 0.047496 QLxxRQ HHhhCC1.0 0.0 1.0 5.045279 1.0683e−16 1.00000 B 1.000000 0.037800 ERxxAMCCccCC 1.0 0.0 1.0 5.111929 1.0693e−16 1.00000 B 1.000000 0.036857LLxxDN HHhhHC 1.0 0.0 1.0 5.969702 1.0799e−16 1.00000 B 1.0000000.027295 DDxxFV CCccCE 1.0 0.0 1.0 6.356999 1.0834e−16 1.00000 B1.000000 0.024148 GSxxAE CEecCE 1.0 0.0 1.0 7.378896 1.0902e−16 1.00000B 1.000000 0.018035 ITxxVF ECccEE 1.0 0.0 1.0 8.484434 1.0950e−161.00000 B 1.000000 0.013701 SSxxVD HCeeEE 40.7 12.3 215.6 8.3114021.6093e−16 1.00000 N 0.188776 0.057261 QGxxLG CCccHH 9.0 0.2 9.321.852434 4.1091e−16 1.00000 B 0.967742 0.017891 RIxxNL HHhhHH 16.5 1.044.0 15.841191 4.4922e−16 1.00000 B 0.375000 0.022308 CHxxYR HHhhHC 10.00.3 10.0 17.416672 1.0961e−15 1.00000 B 1.000000 0.031914 VAxxNG ECccCC21.6 2.4 46.6 12.569376 1.5977e−15 1.00000 B 0.463519 0.052575 LDxxGKCCccCH 11.3 0.3 39.1 20.968186 2.4107e−15 1.00000 B 0.289003 0.007117SWxxGC EEccCC 15.3 0.8 129.4 15.971916 6.7763e−15 1.00000 B 0.1182380.006387 SGxxKS CCccHH 20.0 2.0 75.4 12.863878 7.1564e−15 1.00000 B0.265252 0.026650 WKxxFT HHhcCC 9.4 0.2 14.5 22.543920 7.4766e−151.00000 B 0.648276 0.011698 QTxxGK CCccCH 13.5 0.6 41.8 16.1897132.0888e−14 1.00000 B 0.322967 0.015328 NTxxDK CEeeEE 28.8 7.8 135.97.708178 2.6509e−14 1.00000 N 0.211921 0.057719 RMxxFK HHccCC 9.5 0.210.7 18.948412 2.7945e−14 1.00000 B 0.887850 0.022821 KCxxCH HCccCC 10.60.4 12.6 17.091511 2.8775e−14 1.00000 B 0.841270 0.029296 LGxxIV CCeeEE9.3 0.2 37.1 21.972185 8.4861e−14 1.00000 B 0.250674 0.004672 CLxxICECccCC 6.0 0.0 9.0 35.053684 9.5349e−14 1.00000 B 0.666667 0.003234YHxxNE HHhhHH 19.5 2.4 46.3 11.422064 2.0039e−13 1.00000 B 0.4211660.051197 LVxxHE HHhhHH 8.9 0.1 52.2 23.129204 2.5855e−13 1.00000 B0.170498 0.002753 IVxxTP ECccCC 9.3 0.2 23.0 19.542690 3.1552e−131.00000 B 0.404348 0.009480 LDxxGK ECccCH 7.3 0.1 6.4 28.4787463.3239e−13 1.00000 B 1.140625 0.007829 GKxxAH CHhhHH 10.0 0.4 9.114.125237 6.7470e−13 1.00000 B 1.098901 0.043619 DNxxKT CCccHH 10.3 0.416.6 15.371814 9.7383e−13 1.00000 B 0.620482 0.025519 CSxxIG CCccCH 4.80.0 11.4 73.811659 1.4691e−12 1.00000 B 0.421053 0.000370 ATxxRV CCchHH8.3 0.2 7.7 19.415438 1.7742e−12 1.00000 B 1.077922 0.020018 QCxxCHHHhhHH 13.0 1.0 22.0 12.026076 1.9167e−12 1.00000 B 0.590909 0.047197DGxxGK CCccCH 15.5 1.3 97.0 12.448014 2.8267e−12 1.00000 B 0.1597940.013569 ACxxDS CCccCC 9.1 0.2 75.1 18.214718 3.0063e−12 1.00000 B0.121172 0.003162 GSxxTT CCchHH 11.2 0.6 31.0 14.187378 4.0789e−121.00000 B 0.361290 0.018443 LGxxCR CCccCH 5.5 0.0 10.3 37.0326776.6138e−12 1.00000 B 0.533981 0.002129 GTxxTF CCchHH 8.0 0.2 12.816.365802 1.0631e−11 1.00000 B 0.625000 0.017934 SSxxNT CCccHH 7.0 0.16.5 21.121389 1.2770e−11 1.00000 B 1.076923 0.014361 AAxxTT CCchHH 9.00.3 18.3 14.828063 1.6044e−11 1.00000 B 0.491803 0.018968 NAxxTT CCchHH9.3 0.3 26.0 15.589019 1.7742e−11 1.00000 B 0.357692 0.012886 SPxxLSECceEE 30.0 9.7 170.2 6.744862 2.3659e−11 1.00000 N 0.176263 0.056698GVxxSA CCchHH 13.4 1.1 67.0 12.144064 2.4899e−11 1.00000 B 0.2000000.015680 FPxxLT HHhhHH 19.4 3.0 59.9 9.792754 2.7723e−11 1.00000 B0.323873 0.049478 KNxxCK EEecCC 13.7 1.2 42.0 11.504674 3.8780e−111.00000 B 0.326190 0.028883 DSxxGK CCccCH 11.3 0.7 45.5 12.8726794.9903e−11 1.00000 B 0.248352 0.015161 PGxxAL CChhHC 10.3 0.7 15.511.892512 7.8512e−11 1.00000 B 0.664516 0.044128 PSxxGK CCccCH 8.0 0.233.5 15.968086 8.7729e−11 1.00000 B 0.238806 0.007104 QGxxKT CCccHH 6.20.1 11.9 20.953421 9.3677e−11 1.00000 B 0.521008 0.007207 AKxxNF CCccCE7.3 0.2 20.8 18.084245 9.7158e−11 1.00000 B 0.350962 0.007557 NDxxGGCChhHC 8.6 0.4 12.7 14.018717 1.3495e−10 1.00000 B 0.677165 0.028017RIxxYT EEccCC 9.0 0.4 49.0 13.900228 1.8474e−10 1.00000 B 0.1836730.007898 DAxxKT CCccHH 9.0 0.4 20.0 12.940407 1.8643e−10 1.00000 B0.450000 0.022343 HHxxLP EEeeCC 4.4 0.0 9.4 41.428721 1.9001e−10 1.00000B 0.468085 0.001195 VSxxCI HHccCH 4.0 0.0 6.0 36.564258 2.3293e−101.00000 B 0.666667 0.001987 PNxxGK CCccCH 7.0 0.2 25.1 16.4899793.2368e−10 1.00000 B 0.278884 0.006877 QTxxAK HHhhHH 11.5 0.9 25.111.041981 3.3849e−10 1.00000 B 0.458167 0.037806 GQxxMS CCchHH 5.0 0.15.0 19.598731 3.5034e−10 1.00000 B 1.000000 0.012850 EAxxAE HHhhHH 21.24.2 95.4 8.498906 7.3395e−10 1.00000 B 0.222222 0.043919 DNxxVP CChhHH5.3 0.0 4.0 27.167952 8.4410e−10 1.00000 B 1.325000 0.005390 QCxxCWCCecHH 4.2 0.0 9.5 34.016093 8.4522e−10 1.00000 B 0.442105 0.001596MExxTL EEccCC 7.0 0.3 9.1 13.024031 8.9179e−10 1.00000 B 0.7692310.030212 QCxxCW CCccHH 4.8 0.0 20.2 33.654743 1.0099e−09 1.00000 B0.237624 0.001000 GLxxWK EEccCC 6.2 0.1 13.4 16.284448 2.1044e−091.00000 B 0.462687 0.010444 TVxxNE CHhhHH 8.8 0.6 11.6 11.1430082.1359e−09 1.00000 B 0.758621 0.049430 QVxxYG CCccHH 6.8 0.2 7.113.693903 2.2761e−09 1.00000 B 0.957746 0.033465 NQxxNR HHchHH 12.9 1.547.3 9.598831 2.8315e−09 1.00000 B 0.272727 0.030964 WGxxYA CCccHH 5.00.0 4.0 22.841046 3.3515e−09 1.00000 B 1.250000 0.007609 VQxxGS ECccCC20.1 4.1 109.8 8.109442 3.6024e−09 1.00000 B 0.183060 0.036992 TWxxGEEEccCE 6.5 0.2 7.5 13.828612 3.7039e−09 1.00000 B 0.866667 0.028366PGxxKG CCccHH 10.8 0.9 34.8 10.398182 4.1662e−09 1.00000 B 0.3103450.026618 TDxxAW CChhHH 15.5 2.5 46.1 8.533841 5.0000e−09 1.00000 B0.336226 0.053469 GAxxTT CCchHH 9.0 0.6 23.9 10.640696 5.7397e−091.00000 B 0.376569 0.026564 GLxxSI ECceEE 5.5 0.1 6.2 16.6592215.8987e−09 1.00000 B 0.887097 0.017201 GVxxSN CCchHH 6.3 0.2 13.014.762570 6.5204e−09 1.00000 B 0.484615 0.013424 SNxxNA HHhhHH 9.7 0.725.5 10.702628 6.6082e−09 1.00000 B 0.380392 0.028390 GYxxNF CCccCC 8.80.6 19.7 10.906559 1.1072e−08 1.00000 B 0.446701 0.029682 ACxxCH CChhHH6.0 0.1 5.0 13.761477 1.1262e−08 1.00000 B 1.200000 0.025723 NAxxSDHHhhHH 9.5 0.8 17.0 9.892985 1.1291e−08 1.00000 B 0.558824 0.047657GDxxDI CCccCH 6.0 0.2 10.7 13.237708 1.2867e−08 1.00000 B 0.5607480.018302 NSxxTT CCchHH 6.5 0.2 9.0 13.069026 1.2875e−08 1.00000 B0.722222 0.026213 GCxxCH CHhhCC 9.2 0.7 22.6 10.113297 1.3219e−081.00000 B 0.407080 0.032100 LTxxHY CEecCC 5.0 0.1 8.0 15.9320221.3450e−08 1.00000 B 0.625000 0.011987 TCxxCH HHhhHH 8.8 0.6 17.110.560727 1.3572e−08 1.00000 B 0.514620 0.036390 GVxxSS CCchHH 8.0 0.522.6 10.763572 1.6961e−08 1.00000 B 0.353982 0.021985 MCxxAL EEchHH 5.70.1 5.0 13.068806 1.8614e−08 1.00000 B 1.140000 0.028442

TABLE 30 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySTxVxK CEeEeE 64.0 12.0 256.9 15.417593 6.1069e−53 1.00000 N 0.2491240.046526 GSxKxT CCcHhH 34.1 0.8 86.9 37.367230 5.6913e−46 1.00000 B0.392405 0.009223 TKxDxK EEeEeE 66.5 16.5 338.4 12.643443 3.0096e−361.00000 N 0.196513 0.048650 TQxGxT CCcChH 18.0 0.2 17.2 35.3336172.8357e−32 1.00000 B 1.046512 0.013590 CKxGxT CCcCcC 27.2 1.1 50.025.153537 9.5225e−32 1.00000 B 0.544000 0.022017 VAxKxG ECcCcC 31.1 2.250.4 20.175102 6.0519e−30 1.00000 B 0.617063 0.042673 CSxGxG CCcCcH 10.30.0 36.8 75.277474 2.5489e−25 1.00000 B 0.279891 0.000507 FPxHxA CCcHhH11.6 0.1 14.2 36.450813 4.1020e−22 1.00000 B 0.816901 0.007059 SSxKxDHCeEeE 38.9 9.5 196.6 9.744738 4.9097e−22 1.00000 N 0.197864 0.048527PTxNxG CEeCcC 15.5 0.1 11.5 30.180949 2.1746e−21 1.00000 B 1.3478260.012468 AAxKxT CCcHhH 13.1 0.2 24.7 27.588401 7.5720e−21 1.00000 B0.530364 0.008904 GAxKxT CCcHhH 18.7 0.8 60.0 20.216935 2.7607e−201.00000 B 0.311667 0.013248 YAxGxT HHcCcC 18.8 0.9 34.2 18.5788253.4934e−20 1.00000 B 0.549708 0.027763 SAxIxR CCcCcH 9.7 0.0 14.744.440313 4.2337e−20 1.00000 B 0.659864 0.003220 NTxVxK CEeEeE 29.8 6.7140.9 9.196737 1.1483e−19 1.00000 N 0.211498 0.047197 GVxKxS CCcHhH 14.00.3 41.2 23.421845 2.3634e−19 1.00000 B 0.339806 0.008322 ACxGxS CCcCcC12.1 0.2 75.0 29.273930 2.9742e−19 1.00000 B 0.161333 0.002221 GVxKxACCcHhH 14.4 0.4 55.7 21.200156 8.0469e−18 1.00000 B 0.258528 0.007849LDxAxK CCcCcH 10.3 0.1 31.5 30.561504 1.0872e−17 1.00000 B 0.3269840.003541 FKxSxF HCcCcC 1.0 0.0 1.0 5.225860 1.0710e−16 1.00000 B1.000000 0.035324 ADxLxP EEcCcC 1.7 0.0 1.0 6.058130 1.0808e−16 1.00000B 1.700000 0.026525 ASxNxY CEhHhH 1.0 0.0 1.0 6.128737 1.0814e−161.00000 B 1.000000 0.025933 EAxRxT HHcCcH 1.0 0.0 1.0 8.2160781.0940e−16 1.00000 B 1.000000 0.014598 SAxVxR CCcChH 8.3 0.1 18.135.643410 1.8927e−16 1.00000 B 0.458564 0.002966 VSxGxG EEeCcC 15.7 0.7142.8 17.308385 8.3711e−16 1.00000 B 0.109944 0.005252 GTxKxF CCcHhH 8.00.1 9.8 27.471521 9.4328e−16 1.00000 B 0.816327 0.008546 TGxGxT CCcChH24.5 3.1 86.8 12.456089 1.4644e−15 1.00000 B 0.282258 0.035354 QTxTxKCCcCcH 7.5 0.1 11.0 31.920048 1.2186e−14 1.00000 B 0.681818 0.004971MExCxL EEcCcC 7.0 0.1 9.1 27.627578 3.2583e−14 1.00000 B 0.7692310.006976 DNxGxT CCcChH 10.3 0.3 15.9 17.812272 5.0703e−14 1.00000 B0.647799 0.020148 RMxTxK HHcCcC 9.5 0.3 10.8 18.244981 5.8055e−141.00000 B 0.879630 0.024326 CLxNxC ECcCcC 6.5 0.0 10.0 38.0990276.1079e−14 1.00000 B 0.650000 0.002893 GLxFxI ECcEeE 7.2 0.1 7.924.637453 8.3971e−14 1.00000 B 0.911392 0.010673 NWxRxV CHhHhH 7.3 0.121.0 29.076095 1.5643e−13 1.00000 B 0.347619 0.002959 SAxIxR CCcChH 7.30.1 20.6 28.942731 1.6267e−13 1.00000 B 0.354369 0.003045 LDxAxK ECcCcH7.0 0.0 5.5 43.537246 2.7400e−13 1.00000 B 1.272727 0.002893 NAxKxTCCcHhH 9.3 0.2 16.7 18.667715 3.1319e−13 1.00000 B 0.556886 0.014312SGxGxS CCcChH 20.0 2.4 84.1 11.420009 3.1854e−13 1.00000 B 0.2378120.028966 TPxLxK CCcCcH 9.1 0.2 18.4 18.736598 3.4040e−13 1.00000 B0.494565 0.012340 DGxTxK CCcCcH 8.0 0.1 29.0 22.438199 4.3553e−131.00000 B 0.275862 0.004267 NVxCxN EEcCcC 14.3 1.0 43.1 13.2146496.2025e−13 1.00000 B 0.331787 0.023961 SSxGxT CCcChH 8.0 0.2 11.018.713621 7.2943e−13 1.00000 B 0.727273 0.016145 TQxPxS EEeCcE 25.8 6.9245.4 7.260776 7.8442e−13 1.00000 N 0.105134 0.028289 GVxKxN CCcHhH 6.30.1 12.0 26.995054 5.1295e−12 1.00000 B 0.525000 0.004482 GGxWxF CCcEeE5.5 0.0 12.0 37.207253 7.6246e−12 1.00000 B 0.458333 0.001810 NVxKxSCCcHhH 7.5 0.2 10.3 18.894023 1.2990e−11 1.00000 B 0.728155 0.014900DAxGxT CCcChH 9.0 0.4 18.0 14.731130 1.7133e−11 1.00000 B 0.5000000.019530 NSxKxT CCcHhH 6.5 0.1 9.0 21.907899 3.2501e−11 1.00000 B0.722222 0.009615 IVxYxP ECcCcC 10.3 0.6 23.0 13.217500 4.2034e−111.00000 B 0.447826 0.024211 RIxNxT EEcCcC 9.0 0.3 49.0 15.0350395.1668e−11 1.00000 B 0.183673 0.006826 KCxAxH HCcCcC 7.0 0.1 6.117.691757 5.5611e−11 1.00000 B 1.147541 0.019116 RLxPxE HCcChH 8.0 0.48.5 12.478417 6.3808e−11 1.00000 B 0.941176 0.045861 GQxIxS CCcHhH 7.00.2 9.0 15.467350 8.5625e−11 1.00000 B 0.777778 0.021972 GDxHxI CCcCcH6.0 0.1 6.2 16.372862 1.4245e−10 1.00000 B 0.967742 0.021171 SWxRxCEEcCcC 4.3 0.0 5.3 36.955945 2.1112e−10 1.00000 B 0.811321 0.002545DSxVxK CCcCcH 8.3 0.3 37.5 15.339191 2.1634e−10 1.00000 B 0.2213330.007352 FTxAxN CChHhH 7.8 0.3 13.0 15.243971 3.2013e−10 1.00000 B0.600000 0.019239 HHxExP EEeEcC 5.4 0.0 9.4 24.178681 3.9133e−10 1.00000B 0.574468 0.005237 NQxPxR HHcHhH 12.9 1.3 49.2 10.416783 6.2879e−101.00000 B 0.262195 0.025975 RGxGxG CCcChH 11.5 1.0 29.8 10.6321469.6622e−10 1.00000 B 0.385906 0.033823 PNxSxK CCcCcH 5.0 0.1 10.121.548123 1.0440e−09 1.00000 B 0.495050 0.005246 EExGxW CCcCcE 6.0 0.111.1 16.481972 1.1317e−09 1.00000 B 0.540541 0.011567 SPxSxS ECcEeE 19.55.5 115.4 6.119672 1.8049e−09 1.00000 N 0.168977 0.047638 EFxFxD CCcCcC9.7 0.7 16.0 10.750240 2.3506e−09 1.00000 B 0.606250 0.045597 QGxGxGCCcChH 8.5 0.5 15.0 11.884559 2.5652e−09 1.00000 B 0.566667 0.031413GTxKxT CCcHhH 9.0 0.5 53.1 11.802594 2.5828e−09 1.00000 B 0.1694920.009815 LGxIxR CCcCcH 4.0 0.0 7.8 27.243385 3.4482e−09 1.00000 B0.512821 0.002742 SDxAxN ECcCcC 6.0 0.2 8.0 13.656497 4.1912e−09 1.00000B 0.750000 0.023197 KNxFxV HHcCcH 6.3 0.2 8.0 13.833088 4.5236e−091.00000 B 0.787500 0.024933 CSxGxG CCcCcC 8.3 0.4 31.0 12.0384136.1081e−09 1.00000 B 0.267742 0.013971 LGxSxV CCeEeE 6.0 0.1 20.215.206575 6.1464e−09 1.00000 B 0.297030 0.007383 NYxPxL CCcCcC 11.1 1.137.6 9.595732 7.2007e−09 1.00000 B 0.295213 0.029674 SCxQxT CCcEeE 10.10.9 32.0 10.049367 7.2459e−09 1.00000 B 0.315625 0.027111 NRxKxT HHcCcC14.5 2.2 44.1 8.614814 7.3085e−09 1.00000 B 0.328798 0.048936 GFxIxGCEeEeE 6.5 0.2 34.1 15.573549 8.3341e−09 1.00000 B 0.190616 0.004874QVxGxG CCcChH 6.8 0.3 7.1 12.055621 9.8300e−09 1.00000 B 0.9577460.042727 QRxGxG CCcChH 9.0 0.7 19.0 9.982543 9.9913e−09 1.00000 B0.473684 0.037666 KNxAxK EEeCcC 13.7 1.9 42.0 8.661753 1.1168e−081.00000 B 0.326190 0.046053 QAxCxQ HHhHhC 11.3 1.2 45.4 9.4393941.3106e−08 1.00000 B 0.248899 0.025993 STxExT EEeEeE 11.4 1.3 30.49.145725 1.3944e−08 1.00000 B 0.375000 0.042057 KDxRxE CCcCcC 9.8 0.823.0 9.956334 1.4414e−08 1.00000 B 0.426087 0.036543 GHxYxT CCcHhH 6.00.1 5.1 13.618973 1.5371e−08 1.00000 B 1.176471 0.026761 YRxLxV HCcEeE5.0 0.1 5.0 13.141823 1.7633e−08 1.00000 B 1.000000 0.028136 PGxGxGCCcChH 10.8 1.1 38.1 9.489389 2.0316e−08 1.00000 B 0.283465 0.028342RExGxS EEcCcC 11.3 1.2 49.0 9.175646 2.2602e−08 1.00000 B 0.2306120.025193 GTxKxC CCcHhH 4.0 0.0 7.1 20.814784 2.5870e−08 1.00000 B0.563380 0.005133 QCxSxW CCcChH 4.4 0.0 23.8 23.337447 2.8327e−081.00000 B 0.184874 0.001472 TAxLxL ECcCeE 3.0 0.0 4.0 33.8454372.9972e−08 1.00000 B 0.750000 0.001958 SGxGxT CCcChH 13.9 2.1 76.18.298731 3.2053e−08 1.00000 B 0.182654 0.027389 KQxTxN CEeEeE 11.7 1.531.3 8.462380 4.9081e−08 1.00000 B 0.373802 0.048588 DKxGxP HHhCcC 15.42.8 61.6 7.726483 5.0446e−08 1.00000 B 0.250000 0.045292 EYxPxG CCcCcC9.3 0.9 25.5 9.162766 7.1809e−08 1.00000 B 0.364706 0.034330 SPxLxDCCcCcC 8.4 0.6 27.7 9.963668 7.7018e−08 1.00000 B 0.303249 0.022499QSxSxL EEcCeE 15.7 2.8 127.3 7.707213 8.1135e−08 1.00000 B 0.1233310.022352 KMxFxL CCcCcC 6.3 0.3 12.6 11.723551 8.2273e−08 1.00000 B0.500000 0.021454 ELxPxR CCcCcE 5.7 0.2 7.0 12.480023 1.1672e−07 1.00000B 0.814286 0.028562 GQxGxC CCcCcH 7.0 0.4 19.7 10.157502 1.2223e−071.00000 B 0.355330 0.021722 TKxFxN EEeEcC 4.4 0.1 8.4 18.0302421.2284e−07 1.00000 B 0.523810 0.006951 QGxGxT CCcChH 6.2 0.3 13.011.287013 1.2372e−07 1.00000 B 0.476923 0.021621

TABLE 31 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySTxVDK CEeEEE 58.1 9.7 253.5 15.835199 1.1831e−55 1.00000 N 0.2291910.038304 TKxDKK EEeEEE 66.1 13.1 336.4 14.928529 8.7974e−50 1.00000 N0.196492 0.038972 SSxKVD HCeEEE 38.4 7.7 196.6 11.327509 3.8624e−291.00000 N 0.195320 0.038973 TQxGKT CCcCHH 15.3 0.2 14.3 32.6299678.9626e−27 1.00000 B 1.069930 0.013253 GSxKST CCcHHH 17.9 0.3 44.031.715529 1.6123e−26 1.00000 B 0.406818 0.007041 SAxIGR CCcCCH 9.7 0.014.7 89.096764 1.6309e−25 1.00000 B 0.659864 0.000805 NTxVDK CEeEEE 28.85.4 135.9 10.341170 2.2370e−24 1.00000 N 0.211921 0.039382 YAxGRT HHcCCC18.3 0.7 30.1 21.449600 1.5545e−22 1.00000 B 0.607973 0.022919 CSxGIGCCcCCC 6.3 0.0 11.9 189.417992 3.9006e−22 1.00000 B 0.529412 0.000093LDxAGK CCcCCH 10.3 0.0 30.5 47.444266 1.7930e−21 1.00000 B 0.3377050.001534 TGxGKT CCcCHH 24.5 1.7 83.7 17.637210 2.4487e−21 1.00000 B0.292712 0.020372 SAxVGR CCcCHH 8.3 0.0 18.1 71.080806 3.2725e−211.00000 B 0.458564 0.000751 SGxGKS CCcCHH 20.0 1.1 73.1 18.6201123.0285e−20 1.00000 B 0.273598 0.014374 PTxNIG CEeCCC 14.3 0.1 10.328.371217 1.6378e−19 1.00000 B 1.388350 0.012635 SAxIGR CCcCHH 7.3 0.020.0 71.573397 5.4679e−19 1.00000 B 0.365000 0.000519 GTxVVG CCcHHH 2.00.0 2.0 11.343455 6.6929e−18 1.00000 B 1.000000 0.015305 VAxKNG ECcCCC20.6 1.6 43.0 15.114508 7.1138e−18 1.00000 B 0.479070 0.038057 GVxKSACCcHHH 12.4 0.2 44.6 24.691608 9.2568e−18 1.00000 B 0.278027 0.005464ACxGDS CCcCCC 9.1 0.1 72.0 37.337944 1.1616e−17 1.00000 B 0.1263890.000815 DNxGKT CCcCHH 10.3 0.1 15.9 26.867787 1.8321e−17 1.00000 B0.647799 0.009068 RSxFLE CCcHHH 1.0 0.0 1.0 5.834083 1.0785e−16 1.00000B 1.000000 0.028542 GTxKPV CCcCCE 1.7 0.0 1.0 6.259571 1.0826e−161.00000 B 1.700000 0.024887 ASxNTY CEhHHH 1.0 0.0 1.0 6.2910021.0829e−16 1.00000 B 1.000000 0.024645 YIxIHA EEcCCC 1.5 0.0 1.06.690226 1.0860e−16 1.00000 B 1.500000 0.021854 DDxRFV CCcCCE 1.0 0.01.0 7.147748 1.0889e−16 1.00000 B 1.000000 0.019197 GYxDNG CCeEEE 1.00.0 1.0 19.741459 1.1074e−16 1.00000 B 1.000000 0.002559 DGxTGK CCcCCH8.0 0.0 29.0 37.332124 1.5231e−16 1.00000 B 0.275862 0.001568 GSxKTTCCcHHH 11.2 0.2 31.0 23.154082 1.8616e−16 1.00000 B 0.361290 0.007299NAxKTT CCcHHH 9.3 0.1 14.1 26.923386 2.8401e−16 1.00000 B 0.6595740.008319 CSxGVG CCcCCH 5.8 0.0 16.0 101.911600 2.9554e−16 1.00000 B0.362500 0.000202 CLxNIC ECcCCC 6.0 0.0 9.0 54.727710 4.6743e−16 1.00000B 0.666667 0.001332 DAxGKT CCcCHH 9.0 0.1 18.0 25.724945 1.1942e−151.00000 B 0.500000 0.006664 GTxKTF CCcHHH 8.0 0.1 9.8 25.3266023.3955e−15 1.00000 B 0.816327 0.010033 AAxKTT CCcHHH 9.0 0.1 18.023.672806 5.1140e−15 1.00000 B 0.500000 0.007842 RMxTFK HHcCCC 9.5 0.210.7 20.171854 9.3741e−15 1.00000 B 0.887850 0.020204 LDxAGK ECcCCH 7.00.0 5.5 57.251217 1.7841e−14 1.00000 B 1.272727 0.001675 GAxKTT CCcHHH9.0 0.2 17.1 21.498820 2.3496e−14 1.00000 B 0.526316 0.009963 IVxYTPECcCCC 9.3 0.2 22.0 21.346526 6.3228e−14 1.00000 B 0.422727 0.008360CSxGIG CCcCCH 4.5 0.0 11.4 110.094950 8.9687e−14 1.00000 B 0.3947370.000146 QTxTGK CCcCCH 7.5 0.1 10.0 26.708621 1.0200e−13 1.00000 B0.750000 0.007783 MExCTL EEcCCC 7.0 0.1 9.1 23.929635 2.3636e−13 1.00000B 0.769231 0.009264 GVxKSS CCcHHH 8.0 0.1 18.1 21.088337 5.5327e−131.00000 B 0.441989 0.007735 GQxIMS CCcHHH 5.0 0.0 5.0 37.1087696.1975e−13 1.00000 B 1.000000 0.003618 PNxSGK CCcCCH 5.0 0.0 10.143.402993 1.0258e−12 1.00000 B 0.495050 0.001309 SSxGNT CCcCHH 7.0 0.16.0 23.356780 1.6575e−12 1.00000 B 1.166667 0.010879 DSxVGK CCcCCH 8.30.2 37.5 20.844667 2.1531e−12 1.00000 B 0.221333 0.004090 LGxSIV CCeEEE6.0 0.0 14.0 27.547447 4.1259e−12 1.00000 B 0.428571 0.003347 LGxICRCCcCCH 4.0 0.0 7.8 63.205494 4.2449e−12 1.00000 B 0.512821 0.000513NVxCKN EEcCCC 13.3 1.0 43.0 12.198471 1.2220e−11 1.00000 B 0.3093020.024087 GVxKSN CCcHHH 6.3 0.1 11.0 23.749628 1.9657e−11 1.00000 B0.572727 0.006297 KNxACK EEeCCC 13.7 1.1 42.0 11.874518 1.9766e−111.00000 B 0.326190 0.027349 RIxNYT EEcCCC 9.0 0.3 46.0 15.3368043.5576e−11 1.00000 B 0.195652 0.007009 QCxSCW CCcCHH 4.4 0.0 20.252.509392 4.3647e−11 1.00000 B 0.217822 0.000347 KCxACH HCcCCC 7.0 0.16.1 17.744020 5.3714e−11 1.00000 B 1.147541 0.019006 PGxGKG CCcCHH 10.80.6 32.8 13.331730 5.3905e−11 1.00000 B 0.329268 0.018189 VDxGKT CCcCHH7.0 0.1 27.3 18.303355 8.7340e−11 1.00000 B 0.256410 0.005170 GDxHDICCcCCH 6.0 0.1 6.1 16.814988 9.2109e−11 1.00000 B 0.983607 0.020432NSxKTT CCcHHH 6.5 0.1 9.0 20.025056 9.3279e−11 1.00000 B 0.7222220.011469 PSxSGK CCcCCH 4.0 0.0 8.0 42.041347 1.1281e−10 1.00000 B0.500000 0.001128 NQxPNR HHcHHH 12.9 1.1 47.4 11.218153 1.4078e−101.00000 B 0.272152 0.023798 QGxGKT CCcCHH 6.2 0.1 12.0 19.8458161.7918e−10 1.00000 B 0.516667 0.007948 GGxGKT CCcCHH 9.0 0.4 41.413.504582 2.5790e−10 1.00000 B 0.217391 0.009873 EQxVGK CCcCCH 4.0 0.010.0 38.073494 3.0463e−10 1.00000 B 0.400000 0.001099 SWxRGC EEcCCC 4.30.0 5.3 33.870887 4.2263e−10 1.00000 B 0.811321 0.003027 LSxAGK CCcCCH4.0 0.0 4.9 30.417945 6.6469e−10 1.00000 B 0.816327 0.003511 QVxGYGCCcCHH 6.8 0.2 7.1 15.043578 7.6627e−10 1.00000 B 0.957746 0.027904VSxGCI HHcCCH 4.0 0.0 6.0 31.335851 7.9497e−10 1.00000 B 0.6666670.002701 HHxELP EEeECC 4.4 0.0 9.4 34.320537 8.4881e−10 1.00000 B0.468085 0.001739 TPxLPK CCcCCH 7.5 0.2 18.0 14.918687 1.0677e−091.00000 B 0.416667 0.013334 ALxVPD CCcCCC 6.0 0.2 7.0 14.2318121.5040e−09 1.00000 B 0.857143 0.024560 QAxSGL HHhHHH 3.0 0.0 8.155.954042 2.5977e−09 1.00000 B 0.370370 0.000354 HKxQSP HHhCCC 5.3 0.17.1 18.695085 2.7215e−09 1.00000 B 0.746479 0.011109 LNxGMV CEeEEE 3.30.0 5.0 52.849045 3.3003e−09 1.00000 B 0.660000 0.000779 KNxFTV HHcCCH6.3 0.2 8.1 14.221970 3.4346e−09 1.00000 B 0.777778 0.023338 RGxGIGCCcCHH 6.2 0.2 9.1 14.500182 3.6936e−09 1.00000 B 0.681319 0.019340PNxGKT CCcCHH 7.0 0.3 11.1 12.297662 3.8566e−09 1.00000 B 0.6306310.027457 QGxGIM CCcCHH 4.8 0.0 6.0 24.626370 4.6432e−09 1.00000 B0.800000 0.006272 WGxGYA CCcCHH 5.0 0.0 4.0 21.911256 4.6611e−09 1.00000B 1.250000 0.008263 TGxGKS CCcCHH 8.6 0.5 26.2 12.019779 5.3272e−091.00000 B 0.328244 0.017795 GSxVEK CEeEEE 10.5 0.9 24.4 10.0644935.4015e−09 1.00000 B 0.430328 0.038468 EFxFPD CCcCCC 8.6 0.5 14.011.100589 5.5408e−09 1.00000 B 0.614286 0.039116 VSxGRG EEeCCC 4.3 0.05.3 24.471776 5.5860e−09 1.00000 B 0.811321 0.005776 VExTFP CCcCCC 8.60.6 14.0 11.070664 5.7586e−09 1.00000 B 0.614286 0.039309 GTxKSC CCcHHH4.0 0.0 5.1 23.127532 6.4409e−09 1.00000 B 0.784314 0.005812 SDxAGNECcCCC 6.0 0.1 5.0 14.505782 6.7366e−09 1.00000 B 1.200000 0.023211GAxKTS CCcHHH 4.6 0.0 6.0 24.335291 7.2209e−09 1.00000 B 0.7666670.005899 PNxGKS CCcCHH 8.0 0.4 27.7 11.511517 8.3861e−09 1.00000 B0.288809 0.015827 GYxDNF CCcCCC 7.8 0.4 16.8 12.300028 8.5367e−091.00000 B 0.464286 0.022196 GHxYAT CCcHHH 5.0 0.0 4.0 20.0578049.3926e−09 1.00000 B 1.250000 0.009845 QAxCSQ HHhHHC 11.3 1.2 43.09.514827 1.0843e−08 1.00000 B 0.262791 0.027116 SPxSLS ECcEEE 19.5 4.0104.7 7.844474 1.1598e−08 1.00000 B 0.186246 0.038586 STxAGK CCcCCH 4.60.0 7.1 23.102876 1.3889e−08 1.00000 B 0.647887 0.005519 YRxLVV HCcEEE5.0 0.1 5.0 13.214477 1.6713e−08 1.00000 B 1.000000 0.027836 GLxDWKEEcCCC 5.2 0.1 9.4 16.189053 1.7939e−08 1.00000 B 0.553191 0.010670CGxGGW CCcCHH 3.0 0.0 11.0 41.184265 1.8299e−08 1.00000 B 0.2727270.000481 ELxPLR CCcCCE 5.7 0.2 6.0 14.252520 2.0714e−08 1.00000 B0.950000 0.025894 GVxKTS CCcHHH 6.0 0.2 20.1 13.617286 2.1197e−081.00000 B 0.298507 0.009159 NGxGKS CCcCHH 6.5 0.2 21.0 13.9158162.2105e−08 1.00000 B 0.309524 0.009836 IYxDRL EEcCEE 3.0 0.0 4.035.222300 2.3615e−08 1.00000 B 0.750000 0.001808

TABLE 32 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySTKxxK CEEeeE 60.5 11.8 226.5 14.522757 3.7939e−47 1.00000 N 0.2671080.052292 EVIxxW CCChhH 22.8 0.2 22.5 53.968344 7.7380e−47 1.00000 B1.013333 0.007666 VACxxG ECCccC 33.4 1.2 47.1 29.574227 6.3139e−421.00000 B 0.709130 0.025811 GSGxxT CCChhH 36.1 1.7 102.2 26.4086322.3179e−37 1.00000 B 0.353229 0.016864 TQTxxT CCCchH 18.0 0.3 17.033.543696 8.6327e−32 1.00000 B 1.058824 0.014884 TKVxxK EEEeeE 66.0 18.9393.0 11.088342 2.6474e−28 1.00000 N 0.167939 0.048171 CSAxxG CCCccH11.6 0.0 33.2 68.884804 1.3944e−26 1.00000 B 0.349398 0.000851 PTVVxxGCEEccC 14.5 0.2 12.5 30.902724 4.3313e−23 1.00000 B 1.160000 0.012920SAGxxR CCCchH 13.2 0.2 48.1 33.084486 6.2790e−22 1.00000 B 0.2744280.003242 QSPxxL EECceE 30.2 6.3 250.7 9.604652 2.6407e−21 1.00000 N0.120463 0.025266 YASxxT HHCccC 19.3 1.0 33.0 18.515875 6.1353e−211.00000 B 0.584848 0.030509 AAGxxT CCChhH 13.1 0.3 27.3 25.5837997.7444e−20 1.00000 B 0.479853 0.009321 GLGxxI ECCeeE 9.7 0.1 10.735.901749 3.0417e−19 1.00000 B 0.906542 0.006767 SSTxxD HCEeeE 40.2 11.4216.6 8.739729 4.4322e−18 1.00000 N 0.185596 0.052797 PGHxxL CCHhhC 11.70.3 13.0 21.216128 1.9065e−17 1.00000 B 0.900000 0.022743 NTKxxK CEEeeE29.8 7.3 135.5 8.590840 2.2286e−17 1.00000 N 0.219926 0.053643 ACNxxSCCCccC 7.0 0.0 7.0 38.909066 4.3747e−17 1.00000 B 1.000000 0.004602FHIxxI HCCccE 1.8 0.0 1.0 5.653955 1.0765e−16 1.00000 B 1.8000000.030333 ADKxxP EECccC 1.7 0.0 1.0 5.727191 1.0774e−16 1.00000 B1.700000 0.029585 WGDxxI CCHhhH 1.0 0.0 1.0 6.949056 1.0877e−16 1.00000B 1.000000 0.020288 GVGxxS CCChhH 14.0 0.6 56.6 17.201557 1.3442e−151.00000 B 0.247350 0.010819 NPTxxE CCChhH 24.1 3.0 87.4 12.3128481.9262e−15 1.00000 B 0.275744 0.034700 TGTxxT CCCchH 12.0 0.4 22.817.764571 2.0846e−15 1.00000 B 0.526316 0.018957 CKNxxT CCCccC 16.8 1.247.7 14.763650 3.0318e−15 1.00000 B 0.352201 0.024136 CSAxxG CCCccC 10.00.2 26.4 22.084450 3.3022e−15 1.00000 B 0.378788 0.007518 SWGxxC EECccC15.5 0.8 138.2 16.002815 7.0489e−15 1.00000 B 0.112156 0.006107 NAGxxTCCChhH 9.3 0.2 15.7 22.744011 8.3544e−15 1.00000 B 0.592357 0.010387GAGxxT CCChhH 18.9 1.7 76.7 13.170310 1.7157e−14 1.00000 B 0.2464150.022653 GVGxxA CCChhH 14.4 0.8 63.0 15.725470 1.8748e−14 1.00000 B0.228571 0.012086 ATNxxV CCChhH 8.3 0.2 8.4 20.963833 2.3520e−14 1.00000B 0.988095 0.018311 FPGxxA CCChhH 11.6 0.4 23.0 17.674124 2.5125e−141.00000 B 0.504348 0.017749 SSTxxT CCCchH 7.0 0.1 7.1 23.4072475.9084e−14 1.00000 B 0.985915 0.012435 TVAxxE CHHhhH 14.8 1.1 24.213.272042 6.4829e−14 1.00000 B 0.611570 0.046058 FTVxxN CCHhhH 9.0 0.211.6 17.712530 1.2155e−13 1.00000 B 0.775862 0.021503 SAGxxR CCCccH 8.50.1 23.1 23.814209 1.6932e−13 1.00000 B 0.367965 0.005384 VSWxxG EEEccC13.7 0.7 132.3 15.493865 1.7679e−13 1.00000 B 0.103553 0.005344 CEGxxYEECccC 15.0 1.2 45.9 13.040250 2.4547e−13 1.00000 B 0.326797 0.025189QTGxxK CCCccH 12.2 0.6 38.8 15.210328 3.1614e−13 1.00000 B 0.3144330.015245 DNAxxT CCCchH 9.3 0.3 13.9 17.499545 4.8409e−13 1.00000 B0.669065 0.019531 NWGxxV CHHhhH 7.3 0.1 21.0 26.559055 5.4139e−131.00000 B 0.347619 0.003537 SCQxxS CCCccC 9.4 0.2 76.8 19.9690667.6050e−13 1.00000 B 0.122396 0.002764 KETxxA CCChhH 18.8 2.4 45.110.948289 1.1586e−12 1.00000 B 0.416851 0.052675 NYTxxL CCCccC 10.1 0.433.0 16.312844 1.6032e−12 1.00000 B 0.306061 0.010921 CLGxxC ECCccC 6.50.1 10.0 28.012557 2.3569e−12 1.00000 B 0.650000 0.005325 SGVxxS CCCchH13.3 0.9 37.9 12.867366 3.0001e−12 1.00000 B 0.350923 0.024946 GYSxxNCEChhH 13.0 0.9 42.3 12.842946 3.1635e−12 1.00000 B 0.307329 0.021422LDNxxK CCCccH 7.3 0.1 11.5 20.759587 4.9463e−12 1.00000 B 0.6347830.010510 RIVxxT EECccC 8.8 0.2 24.1 18.473092 6.3694e−12 1.00000 B0.365145 0.009037 DAAxxT CCCchH 9.0 0.3 18.0 15.524576 7.1271e−121.00000 B 0.500000 0.017686 GTGxxF CCChhH 8.0 0.2 12.8 16.6461898.2070e−12 1.00000 B 0.625000 0.017357 LGNxxR CCCccH 5.5 0.0 10.333.262540 1.9184e−11 1.00000 B 0.533981 0.002635 HLCxxH CCCchH 9.8 0.514.2 13.568130 2.9460e−11 1.00000 B 0.690141 0.034352 NQTxxR HHChhH 12.91.0 46.4 12.053151 3.2314e−11 1.00000 B 0.278017 0.021481 IVNxxP ECCccC10.3 0.6 22.0 13.083925 4.5307e−11 1.00000 B 0.468182 0.025815 SPGxxRCCCceE 8.0 0.3 14.9 14.892055 7.0207e−11 1.00000 B 0.536913 0.018402QGSxxT CCCchH 6.2 0.1 11.9 20.206649 1.4310e−10 1.00000 B 0.5210080.007738 MELxxL EECccC 7.0 0.2 10.2 14.733553 2.7272e−10 1.00000 B0.686275 0.021233 NVGxxS CCChhH 8.5 0.4 12.5 13.078561 3.7104e−101.00000 B 0.680000 0.031719 ENDxxG CCChhH 8.6 0.4 12.7 13.0477403.9246e−10 1.00000 B 0.677165 0.032073 GIPxxQ CCChhH 17.9 2.9 69.38.960881 6.8872e−10 1.00000 B 0.258297 0.042109 KTTxxY HHHhhH 10.0 0.737.4 11.632848 7.0627e−10 1.00000 B 0.267380 0.017557 FPExxT HHHhhH 14.21.7 58.9 9.754512 8.2132e−10 1.00000 B 0.241087 0.028739 TGDxxG ECCccC7.1 0.2 30.0 14.821104 1.6564e−09 1.00000 B 0.236667 0.007241 DACxxDECCccC 4.1 0.0 61.8 33.257720 1.7419e−09 1.00000 B 0.066343 0.000244GISxxT CCChhH 10.1 0.8 22.8 10.488750 2.0178e−09 1.00000 B 0.4429820.035657 NMDxxE CCChhH 12.4 1.4 28.5 9.575028 2.1163e−09 1.00000 B0.435088 0.048771 TQSxxS EEEccE 21.5 6.4 177.4 6.065732 2.2502e−091.00000 N 0.121195 0.036167 GLSxxI EEEccC 3.0 0.0 5.0 53.9961552.3408e−09 1.00000 B 0.600000 0.000616 SESxxH CCHhhH 3.5 0.0 5.050.186716 4.5726e−09 1.00000 B 0.700000 0.000971 GHGxxT CCChhH 6.0 0.26.1 11.911470 5.0834e−09 1.00000 B 0.983607 0.039881 NVAxxN EECccC 14.32.1 45.9 8.718869 5.9217e−09 1.00000 B 0.311547 0.044938 ACQxxS CCCccC6.0 0.1 28.6 15.550736 6.0423e−09 1.00000 B 0.209790 0.004986 PSGxxKCCCccH 8.5 0.5 28.6 11.946646 6.5585e−09 1.00000 B 0.297203 0.016094GQGxxS CCChhH 7.0 0.3 11.0 11.597337 8.0172e−09 1.00000 B 0.6363640.030935 DGGxxK CCCccH 9.0 0.6 37.0 10.714724 8.6960e−09 1.00000 B0.243243 0.016807 FQLxxE CCCchH 6.9 0.2 21.0 14.135162 8.7273e−091.00000 B 0.328571 0.010733 TGDxxC CCChhH 5.0 0.1 12.5 17.7507418.8848e−09 1.00000 B 0.400000 0.006191 NSGxxT CCChhH 6.5 0.2 10.013.493999 1.1601e−08 1.00000 B 0.650000 0.022140 HHMxxP EEEecC 4.4 0.08.9 24.318590 1.2380e−08 1.00000 B 0.494382 0.003638 EFDxxD EEChhH 5.40.1 18.0 18.084978 1.2762e−08 1.00000 B 0.300000 0.004819 SCKxxT CCCeeE11.1 1.2 35.0 9.075284 1.6971e−08 1.00000 B 0.317143 0.035046 FSTxxRCHHhhH 9.5 0.9 16.7 9.595533 1.7168e−08 1.00000 B 0.568862 0.051223RETxxS EECccC 11.3 1.2 48.0 9.214567 2.0687e−08 1.00000 B 0.2354170.025551 QGQxxG CCCchH 5.5 0.1 5.2 13.445268 2.0902e−08 1.00000 B1.057692 0.027961 VTCxxG ECCccC 7.2 0.4 13.5 11.251571 2.2708e−081.00000 B 0.533333 0.028014 PNRxxR HHHhhH 12.2 1.5 48.9 8.7133792.4346e−08 1.00000 B 0.249489 0.031581 KNVxxK EEEccC 13.7 2.1 42.08.219845 2.9154e−08 1.00000 B 0.326190 0.049934 KELxxY HHHccC 6.5 0.37.9 11.718695 2.9653e−08 1.00000 B 0.822785 0.036891 KCKxxH HCCccC 5.00.1 6.1 13.620436 3.0526e−08 1.00000 B 0.819672 0.021411 IYRxxL EECceE3.0 0.0 4.0 33.544899 3.1613e−08 1.00000 B 0.750000 0.001993 STVxxTEEEeeE 11.4 1.4 30.4 8.710677 3.1635e−08 1.00000 B 0.375000 0.045559SAAxxR CHHhhH 17.5 3.5 71.0 7.613866 3.2381e−08 1.00000 B 0.2464790.049841 GFSxxD CCChhH 10.6 1.1 34.6 9.262979 3.3221e−08 1.00000 B0.306358 0.031463 QPGxxQ CCHhhH 5.5 0.1 6.9 14.348240 3.4235e−08 1.00000B 0.797101 0.020633 EYAxxG CCCccC 8.2 0.6 21.4 10.124027 4.2668e−081.00000 B 0.383178 0.027198 QHFxxL EEEecE 6.7 0.2 5.8 12.6643664.4726e−08 1.00000 B 1.155172 0.034901 PNGxxK CCCccH 7.0 0.4 21.111.085149 4.4894e−08 1.00000 B 0.331754 0.017280 PTExxL CCHhhH 11.2 1.378.3 8.925828 4.6189e−08 1.00000 B 0.143040 0.016096 PSSxxA CCEeeE 14.12.2 99.1 8.057665 4.7806e−08 1.00000 B 0.142281 0.022428

TABLE 33 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySTKxDK CEEeEE 55.6 8.7 226.6 16.255923 1.6857e−58 1.00000 N 0.2453660.038248 TKVxKK EEEeEE 65.1 13.0 336.5 14.736016 1.5202e−48 1.00000 N0.193462 0.038638 SAGxGR CCCcHH 13.2 0.0 46.1 75.771959 3.4177e−311.00000 B 0.286334 0.000656 SSTxVD HCEeEE 39.7 8.3 215.6 11.1427642.7999e−28 1.00000 N 0.184137 0.038369 CSAxIG CCCcCC 8.5 0.0 11.9146.471121 9.1438e−27 1.00000 B 0.714286 0.000283 TQTxKT CCCcHH 15.3 0.214.3 31.603282 2.1665e−26 1.00000 B 1.069930 0.014116 GSGxST CCChHH 17.90.4 44.9 28.229499 7.9074e−25 1.00000 B 0.398664 0.008645 NTKxDK CEEeEE28.8 5.3 135.4 10.419284 1.0158e−24 1.00000 N 0.212703 0.039113 VACxNGECCcCC 21.6 1.0 44.0 21.151067 8.7514e−24 1.00000 B 0.490909 0.022104YASxRT HHCcCC 17.3 0.7 30.0 20.226529 9.0033e−21 1.00000 B 0.5766670.023008 CSAxVG CCCcCH 6.8 0.0 16.0 121.887300 8.6362e−20 1.00000 B0.425000 0.000194 TGTxKT CCCcHH 12.0 0.2 20.8 25.525015 3.4833e−191.00000 B 0.576923 0.010355 SAGxGR CCCcCH 8.5 0.0 21.6 52.2408446.4657e−19 1.00000 B 0.393519 0.001220 NAGxTT CCChHH 9.3 0.1 13.931.221526 1.9447e−17 1.00000 B 0.669065 0.006303 PTVVxIG CEEcCC 12.3 0.19.3 25.790761 2.7631e−17 1.00000 B 1.322581 0.013789 HIAxVA EEEeCC 3.00.0 1.0 5.254133 1.0714e−16 1.00000 B 3.000000 0.034958 DASxNT CCEhHH1.0 0.0 1.0 6.224344 1.0823e−16 1.00000 B 1.000000 0.025162 GTMxPVCCCcCE 1.7 0.0 1.0 6.428880 1.0840e−16 1.00000 B 1.700000 0.023624GPExSF CHHhCC 1.0 0.0 1.0 7.872524 1.0926e−16 1.00000 B 1.0000000.015879 GYRxNG CCEeEE 1.0 0.0 1.0 18.626022 1.1070e−16 1.00000 B1.000000 0.002874 DNAxKT CCCcHH 9.3 0.1 13.1 27.283943 1.5916e−161.00000 B 0.709924 0.008729 CLGxIC ECCcCC 6.0 0.0 9.0 53.5495106.0640e−16 1.00000 B 0.666667 0.001391 LDNxGK CCCcCH 7.3 0.0 11.538.694812 9.3203e−16 1.00000 B 0.634783 0.003074 AAGxTT CCChHH 9.0 0.118.0 25.941783 1.0307e−15 1.00000 B 0.500000 0.006556 SWGxGC EECcCC 15.30.7 129.4 17.090125 1.1583e−15 1.00000 B 0.118238 0.005648 GVGxSA CCChHH12.4 0.4 45.9 19.796606 1.4383e−15 1.00000 B 0.270153 0.008108 DAAxKTCCCcHH 9.0 0.2 18.0 22.774382 1.0039e−14 1.00000 B 0.500000 0.008457IVNxTP ECCcCC 9.3 0.2 22.0 22.913053 1.8558e−14 1.00000 B 0.4227270.007285 PGHxAL CCHhHC 9.9 0.2 12.9 19.649495 2.1377e−14 1.00000 B0.767442 0.019076 LGNxCR CCCcCH 5.5 0.0 10.3 63.590565 3.0404e−141.00000 B 0.533981 0.000725 ACNxDS CCCcCC 5.0 0.0 6.0 51.9926205.1575e−14 1.00000 B 0.833333 0.001538 CSAxIG CCCcCH 4.8 0.0 9.799.533355 1.1954e−13 1.00000 B 0.494845 0.000240 SGVxKS CCCcHH 11.3 0.432.3 16.917556 1.4040e−13 1.00000 B 0.349845 0.012975 GTGxTF CCChHH 8.00.2 9.8 19.427452 2.1554e−13 1.00000 B 0.816327 0.016880 QTGxGK CCCcCH11.5 0.5 36.8 16.466361 3.1892e−13 1.00000 B 0.312500 0.012378 DGGxGKCCCcCH 9.0 0.2 36.0 19.638787 4.4953e−13 1.00000 B 0.250000 0.005607QGSxKT CCCcHH 6.2 0.0 11.9 32.654707 5.0082e−13 1.00000 B 0.5210080.003004 GSGxTT CCChHH 11.2 0.5 31.1 15.166466 1.1005e−12 1.00000 B0.360129 0.016252 GAGxTT CCChHH 9.0 0.3 16.9 17.041702 1.2312e−121.00000 B 0.532544 0.015789 GVGxSS CCChHH 8.0 0.2 18.0 19.5814951.7118e−12 1.00000 B 0.444444 0.008983 QSPxSL EECcEE 25.0 4.4 183.210.018045 2.8037e−12 1.00000 B 0.136463 0.023753 SSTxNT CCCcHH 7.0 0.16.0 21.807312 3.7412e−12 1.00000 B 1.166667 0.012460 RIVxYT EECcCC 8.80.2 23.1 18.925367 4.1481e−12 1.00000 B 0.380952 0.009004 PSGxGK CCCcCH8.0 0.2 28.7 19.269802 4.4409e−12 1.00000 B 0.278746 0.005792 PNGxGKCCCcCH 7.0 0.1 21.1 21.242037 9.0973e−12 1.00000 B 0.331754 0.005017KNVxCK EEEcCC 13.7 1.1 42.0 12.273416 9.7008e−12 1.00000 B 0.3261900.025822 GAGxTS CCChHH 4.6 0.0 6.0 55.188706 1.0692e−11 1.00000 B0.766667 0.001156 AKRxNF CCCcCE 7.3 0.1 18.3 20.637253 1.3947e−111.00000 B 0.398907 0.006655 NQTxNR HHChHH 12.8 0.9 46.4 12.6916511.5524e−11 1.00000 B 0.275862 0.019330 VSWxRG EEEcCC 4.3 0.0 5.350.560978 1.7337e−11 1.00000 B 0.811321 0.001362 GLGxSI ECCeEE 5.5 0.06.2 29.505444 2.1111e−11 1.00000 B 0.887097 0.005565 ATNxRV CCChHH 8.30.1 6.4 20.022828 2.1648e−11 1.00000 B 1.296875 0.015713 FPExLT HHHhHH14.2 1.3 57.9 11.378309 2.9795e−11 1.00000 B 0.245250 0.022670 GVGxSNCCChHH 6.3 0.1 12.0 21.969649 5.7852e−11 1.00000 B 0.525000 0.006723MELxTL EECcCC 7.0 0.2 9.1 15.541949 8.4461e−11 1.00000 B 0.7692310.021525 LGFxIV CCEeEE 4.3 0.0 7.8 38.805376 2.5905e−10 1.00000 B0.551282 0.001568 GQGxMS CCChHH 5.0 0.1 5.0 19.958451 2.9275e−10 1.00000B 1.000000 0.012396 QGQxIM CCCcHH 4.8 0.0 5.0 29.497827 7.6876e−101.00000 B 0.960000 0.005266 LNVxMV CEEeEE 3.3 0.0 5.0 64.2240841.0266e−09 1.00000 B 0.660000 0.000527 DACxGD ECCcCC 4.1 0.0 61.835.388383 1.0648e−09 1.00000 B 0.066343 0.000216 NVAxKN EECcCC 13.3 1.543.0 9.703826 1.3782e−09 1.00000 B 0.309302 0.035495 GLSxLI EEEcCC 3.00.0 3.0 50.949375 1.5382e−09 1.00000 B 1.000000 0.001154 TVAxNE CHHhHH7.8 0.4 10.6 12.570650 2.3379e−09 1.00000 B 0.735849 0.034194 QCGxCWCCEcHH 4.2 0.0 9.5 29.808739 2.4093e−09 1.00000 B 0.442105 0.002074WGHxYA CCCcHH 5.0 0.0 4.0 23.565216 2.6158e−09 1.00000 B 1.2500000.007152 WKNxFT HHHcCC 5.9 0.1 8.6 17.818038 2.8442e−09 1.00000 B0.686047 0.012446 DSGxGK CCCcCH 8.3 0.4 37.5 12.773489 3.0722e−091.00000 B 0.221333 0.010339 NSGxTT CCChHH 6.5 0.2 9.0 14.8025343.1087e−09 1.00000 B 0.722222 0.020643 GGTxKT CCCcHH 8.0 0.4 31.012.341190 3.4938e−09 1.00000 B 0.258065 0.012435 QCGxCW CCCcHH 4.8 0.020.2 27.916343 4.4457e−09 1.00000 B 0.237624 0.001448 VEFxFP CCCcCC 8.60.5 14.0 11.124863 5.3705e−09 1.00000 B 0.614286 0.038960 GSTxEK CEEeEE10.5 0.9 24.4 10.039871 5.6240e−09 1.00000 B 0.430328 0.038632 KCKxCHHCCcCC 5.0 0.1 5.6 15.673528 5.6390e−09 1.00000 B 0.892857 0.017772EFTxPD CCCcCC 8.6 0.6 14.0 11.007189 6.2511e−09 1.00000 B 0.6142860.039724 GGVxKS CCCcHH 9.1 0.6 54.0 11.185057 6.4450e−09 1.00000 B0.168519 0.010848 YGFxLH CCEeEE 4.0 0.0 4.0 20.720564 7.2597e−09 1.00000B 1.000000 0.009231 GVGxTS CCChHH 6.0 0.2 21.1 14.676187 9.5090e−091.00000 B 0.284360 0.007563 YTPxLP CCCcCC 8.0 0.5 27.6 11.2068641.2161e−08 1.00000 B 0.289855 0.016678 VDHxKT CCCcHH 6.5 0.2 27.314.707293 1.4173e−08 1.00000 B 0.238095 0.006798 QRRxLG CCCcHH 5.0 0.16.0 14.558979 1.5132e−08 1.00000 B 0.833333 0.019131 GISxET CCChHH 7.60.4 14.2 11.660873 1.6894e−08 1.00000 B 0.535211 0.027667 DHGxTT CCChHH6.0 0.2 28.3 14.184164 1.6909e−08 1.00000 B 0.212014 0.006006 SGSxKSCCCcHH 6.7 0.2 20.8 13.652759 2.3784e−08 1.00000 B 0.322115 0.010926HHMxLP EEEeCC 3.4 0.0 8.9 40.330625 2.4388e−08 1.00000 B 0.3820220.000796 INGxSA HHCcHH 5.0 0.2 5.0 12.702857 2.4523e−08 1.00000 B1.000000 0.030055 AGTxKS CCCcHH 4.0 0.0 5.5 19.813123 2.5620e−08 1.00000B 0.727273 0.007316 ELGxLR CCCcCE 5.7 0.2 6.5 14.233671 2.7098e−081.00000 B 0.876923 0.023916 TWNxGE EECcCE 5.5 0.2 5.5 13.5618912.7523e−08 1.00000 B 1.000000 0.029035 GLTxWK EECcCC 5.2 0.1 9.415.432176 2.8452e−08 1.00000 B 0.553191 0.011710 PLRxFK CCEeEE 5.4 0.25.7 13.543717 3.2325e−08 1.00000 B 0.947368 0.027051 ALDxPD CCCcCC 5.50.2 6.0 13.792962 3.3034e−08 1.00000 B 0.916667 0.025696 RVExTF CCCcCC6.9 0.4 9.0 11.165987 3.4462e−08 1.00000 B 0.766667 0.039724 THCxVHCCEeEE 5.0 0.0 3.0 29.548453 4.0150e−08 1.00000 B 1.666667 0.003424GSGxGT CCChHH 6.0 0.2 11.8 12.122485 4.1308e−08 1.00000 B 0.5084750.019576 LGPxRS CCCcEE 5.7 0.2 6.0 13.118801 4.6152e−08 1.00000 B0.950000 0.030406 AAGxST CCChHH 4.1 0.0 6.0 18.903444 4.7469e−08 1.00000B 0.683333 0.007724 TLKxET CCEeEE 6.0 0.3 9.0 11.359947 4.8191e−081.00000 B 0.666667 0.029193 PGSxKG CCCcHH 5.0 0.1 10.1 14.3775065.2693e−08 1.00000 B 0.495050 0.011555 IYRxRL EECcEE 3.0 0.0 4.029.281320 7.1208e−08 1.00000 B 0.750000 0.002613

TABLE 34 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySTKVxK CEEEeE 58.5 9.1 226.5 16.684990 1.4066e−61 1.00000 N 0.2582780.040286 GSGKxT CCCHhH 34.1 0.7 84.7 39.230822 1.9681e−47 1.00000 B0.402597 0.008617 TKVDxK EEEEeE 65.5 14.0 338.5 14.091535 1.4697e−441.00000 N 0.193501 0.041227 VACKxG ECCCcC 31.1 1.2 45.0 27.2131704.3643e−38 1.00000 B 0.691111 0.027516 TQTGxT CCCChH 18.0 0.3 17.033.601240 8.1511e−32 1.00000 B 1.058824 0.014834 CSAGxG CCCCcH 10.3 0.033.2 101.706126 5.3781e−28 1.00000 B 0.310241 0.000308 SSTKxD HCEEeE37.9 8.0 196.6 10.787374 1.3832e−26 1.00000 N 0.192777 0.040721 AAGKxTCCCHhH 13.1 0.1 24.0 44.361614 3.6765e−26 1.00000 B 0.545833 0.003599NTKVxK CEEEeE 29.8 5.6 135.4 10.438853 7.8103e−25 1.00000 N 0.2200890.041391 GVGKxS CCCHhH 14.0 0.1 38.0 36.367233 1.3150e−24 1.00000 B0.368421 0.003834 FPGHxA CCCHhH 10.6 0.1 13.0 38.749603 4.1480e−211.00000 B 0.815385 0.005708 GAGKxT CCCHhH 17.7 0.6 56.1 22.0559398.2545e−21 1.00000 B 0.315508 0.010823 YASGxT HHCCcC 17.3 0.7 30.019.794775 1.7769e−20 1.00000 B 0.576667 0.023963 GVGKxA CCCHhH 13.4 0.249.1 27.315326 8.8595e−20 1.00000 B 0.272912 0.004755 SAGIxR CCCCcH 7.50.0 14.7 72.680577 2.7529e−19 1.00000 B 0.510204 0.000723 PTVVNxG CEECcC13.5 0.1 10.5 27.663655 3.7910e−19 1.00000 B 1.285714 0.013535 DNAGxTCCCChH 9.3 0.1 12.9 37.638562 4.8746e−19 1.00000 B 0.720930 0.004693CSAGxG CCCCcC 7.3 0.0 18.9 67.922555 1.0491e−18 1.00000 B 0.3862430.000610 SAGVxR CCCChH 7.3 0.0 18.1 64.671021 1.9499e−18 1.00000 B0.403315 0.000702 VSWGxG EEECcC 13.7 0.3 111.4 24.500612 3.0198e−181.00000 B 0.122980 0.002692 NAGKxT CCCHhH 9.3 0.1 15.7 34.7984874.6527e−18 1.00000 B 0.592357 0.004501 GLGFxI ECCEeE 7.2 0.0 7.939.857265 1.0617e−16 1.00000 B 0.911392 0.004110 TGGAxI CCCCcE 1.0 0.01.0 5.112750 1.0693e−16 1.00000 B 1.000000 0.036846 RYTQxN CCCCcC 1.00.0 1.0 5.439401 1.0739e−16 1.00000 B 1.000000 0.032694 SLPTxD CCCChH1.0 0.0 1.0 5.557401 1.0754e−16 1.00000 B 1.000000 0.031363 ALASxACCCCcC 1.0 0.0 1.0 5.760690 1.0777e−16 1.00000 B 1.000000 0.029252FHISxI HCCCcE 1.8 0.0 1.0 6.089482 1.0811e−16 1.00000 B 1.8000000.026259 ADKLxP EECCcC 1.7 0.0 1.0 6.188020 1.0820e−16 1.00000 B1.700000 0.025451 LSERxT CCHHhH 1.0 0.0 1.0 6.443344 1.0841e−16 1.00000B 1.000000 0.023520 ELTSxE HHHHhH 1.0 0.0 1.0 7.149093 1.0889e−161.00000 B 1.000000 0.019190 YIKIxA EECCcC 1.5 0.0 1.0 7.8534651.0925e−16 1.00000 B 1.500000 0.015955 KSSTxE ECCCcC 1.0 0.0 1.08.919297 1.0964e−16 1.00000 B 1.000000 0.012414 RSLFxE CCCHhH 1.0 0.01.0 9.393303 1.0978e−16 1.00000 B 1.000000 0.011206 DAAGxT CCCChH 9.00.1 18.0 27.238045 4.3773e−16 1.00000 B 0.500000 0.005957 TGTGxT CCCChH12.0 0.4 20.8 18.661705 4.5887e−16 1.00000 B 0.576923 0.018954 CKNGxTCCCCcC 16.8 1.1 47.2 15.534036 7.2121e−16 1.00000 B 0.355932 0.022272GTGKxF CCCHhH 8.0 0.1 9.8 27.402240 9.8161e−16 1.00000 B 0.8163270.008589 ACNGxS CCCCcC 7.0 0.0 6.0 40.200001 2.5618e−15 1.00000 B1.166667 0.003699 CLGNxC ECCCcC 6.5 0.0 10.0 48.070386 3.8149e−151.00000 B 0.650000 0.001821 MELCxL EECCcC 7.0 0.1 9.1 29.5485591.2860e−14 1.00000 B 0.769231 0.006107 SAGIxR CCCChH 5.9 0.0 20.061.175162 3.3437e−14 1.00000 B 0.295000 0.000464 QTGTxK CCCCcH 7.5 0.110.0 28.782865 3.6338e−14 1.00000 B 0.750000 0.006714 NVACxN EECCcC 14.31.0 43.1 13.792835 2.2413e−13 1.00000 B 0.331787 0.022206 GVGKxN CCCHhH6.3 0.0 12.0 34.262479 3.0452e−13 1.00000 B 0.525000 0.002795 GQGIxSCCCHhH 7.0 0.1 7.0 20.184497 3.9232e−13 1.00000 B 1.000000 0.016891NWGRxV CHHHhH 7.3 0.1 21.0 26.457581 5.7051e−13 1.00000 B 0.3476190.003564 SGVGxS CCCChH 11.3 0.5 32.4 15.771006 5.7870e−13 1.00000 B0.348765 0.014751 TQSPxS EEECcE 21.5 5.1 177.4 7.328957 6.0144e−131.00000 N 0.121195 0.028944 LDNAxK CCCCcH 6.3 0.0 10.5 31.1233637.2899e−13 1.00000 B 0.600000 0.003867 RIVNxT EECCcC 8.8 0.2 22.120.487107 1.1508e−12 1.00000 B 0.398190 0.008079 DGGTxK CCCCcH 8.0 0.229.0 20.047467 2.4564e−12 1.00000 B 0.275862 0.005310 SSTGxT CCCChH 7.00.1 6.0 21.834595 3.6862e−12 1.00000 B 1.166667 0.012429 NVGKxS CCCHhH7.5 0.1 10.0 20.522046 3.7863e−12 1.00000 B 0.750000 0.013066 NYTPxLCCCCcC 10.1 0.4 32.0 15.306066 4.9076e−12 1.00000 B 0.315625 0.012696LGNIxR CCCCcH 4.0 0.0 7.8 60.798179 5.7878e−12 1.00000 B 0.5128210.000554 IVNYxP ECCCcC 10.3 0.5 22.0 13.766180 1.8207e−11 1.00000 B0.468182 0.023508 NQTPxR HHCHhH 12.9 1.0 46.4 12.190145 2.5665e−111.00000 B 0.278017 0.021060 NSGKxT CCCHhH 6.5 0.1 9.0 21.3560624.3860e−11 1.00000 B 0.722222 0.010109 EYAPxG CCCCcC 8.2 0.3 12.314.874800 4.6252e−11 1.00000 B 0.666667 0.023547 FTVAxN CCHHhH 7.8 0.210.6 16.868395 4.6779e−11 1.00000 B 0.735849 0.019497 GTGKxT CCCHhH 9.00.3 53.3 15.122265 4.9805e−11 1.00000 B 0.168856 0.006205 EFTFxD CCCCcC9.7 0.6 14.0 12.314175 1.6790e−10 1.00000 B 0.692857 0.040915 GGTGxTCCCChH 8.0 0.3 31.9 14.944327 2.2386e−10 1.00000 B 0.250784 0.008459QGSGxT CCCChH 6.2 0.1 12.0 18.460914 4.1542e−10 1.00000 B 0.5166670.009153 DSGVxK CCCCcH 8.3 0.3 35.5 14.606079 4.2534e−10 1.00000 B0.233803 0.008518 STVExT EEEEeE 11.4 1.0 24.4 10.715271 5.4506e−101.00000 B 0.467213 0.040350 VDHGxT CCCChH 6.5 0.1 27.3 19.2907506.4666e−10 1.00000 B 0.238095 0.004035 SWGRxC EECCcC 4.3 0.0 5.331.479143 7.5680e−10 1.00000 B 0.811321 0.003503 LSGAxK CCCCcH 4.0 0.04.9 29.310363 8.9269e−10 1.00000 B 0.816327 0.003780 KDYRxE CCCCcC 8.80.5 15.5 12.425669 1.0646e−09 1.00000 B 0.567742 0.029933 KNVAxK EEECcC13.7 1.6 42.0 9.724955 1.2122e−09 1.00000 B 0.326190 0.038278 SGSGxSCCCChH 6.7 0.1 19.8 17.619560 1.2663e−09 1.00000 B 0.338384 0.007051PNGSxK CCCCcH 5.0 0.1 10.1 19.647202 2.5756e−09 1.00000 B 0.4950500.006290 EEGGxW CCCCcE 5.5 0.1 9.0 19.744546 2.6631e−09 1.00000 B0.611111 0.008456 KCKAxH HCCCcC 5.0 0.1 5.1 16.064817 2.7922e−09 1.00000B 0.980392 0.018626 NVGKxT CCCHhH 6.0 0.1 18.0 15.931018 3.2649e−091.00000 B 0.333333 0.007583 LNVGxV CEEEeE 3.3 0.0 7.7 51.4725875.1796e−09 1.00000 B 0.428571 0.000533 GAGKxS CCCHhH 4.6 0.0 10.026.804049 6.0243e−09 1.00000 B 0.460000 0.002916 DKEGxP HHHCcC 14.5 2.153.1 8.707830 7.6359e−09 1.00000 B 0.273070 0.039712 TVAQxE CHHHhH 8.30.5 21.0 11.382891 8.6178e−09 1.00000 B 0.395238 0.022987 VEFTxP CCCCcC8.6 0.6 14.0 10.667799 9.7558e−09 1.00000 B 0.614286 0.042052 GHGYxTCCCHhH 6.0 0.1 5.1 14.266534 9.7778e−09 1.00000 B 1.176471 0.024445GSTVxK CEEEeE 10.5 1.0 24.4 9.702377 9.8438e−09 1.00000 B 0.4303280.040973 SCKQxT CCCEeE 10.1 0.9 32.0 9.840061 1.0197e−08 1.00000 B0.315625 0.028110 RETGxS EECCcC 11.3 1.2 48.0 9.552671 1.1284e−081.00000 B 0.235417 0.024074 NGSGxS CCCChH 5.0 0.1 13.1 17.1537491.2945e−08 1.00000 B 0.381679 0.006313 HHMExP EEEEcC 4.4 0.0 8.923.470902 1.6376e−08 1.00000 B 0.494382 0.003902 DHGKxT CCCHhH 6.0 0.231.9 14.277130 1.6708e−08 1.00000 B 0.188088 0.005259 SPGAxR CCCCeE 6.00.2 10.9 12.858950 1.8510e−08 1.00000 B 0.550459 0.018981 ACIAxE CCCCcC6.3 0.3 7.0 11.516135 2.1334e−08 1.00000 B 0.900000 0.040631 ELGPxRCCCCcE 5.7 0.2 6.0 14.099971 2.2990e−08 1.00000 B 0.950000 0.026441QHFKxL EEEEcE 6.7 0.2 5.8 13.135377 3.1489e−08 1.00000 B 1.1551720.032522 DLEAxG EEEEcC 2.2 0.0 4.0 119.847863 3.4045e−08 1.00000 B0.550000 0.000084 RSFKxF EEEEeE 5.4 0.2 5.7 13.424145 3.5216e−08 1.00000B 0.947368 0.027520 SVGKxS CCCHhH 4.0 0.0 13.0 21.268702 3.6221e−081.00000 B 0.307692 0.002681 IYRDxL EECCeE 3.0 0.0 4.0 32.5858743.7597e−08 1.00000 B 0.750000 0.002112 PNVGxS CCCChH 6.0 0.2 19.412.859611 3.8924e−08 1.00000 B 0.309278 0.010579 GTGKxC CCCHhH 4.0 0.06.1 18.981083 4.3099e−08 1.00000 B 0.655738 0.007173 GPLRxF CCCEeE 5.50.2 5.8 13.124718 4.6797e−08 1.00000 B 0.948276 0.029294

TABLE 35 In Expected in P-Value P-Value Observed Null Sequence StructureEpitopes Epi In PDB Z-Score Upper Lower Distribution Ratio ProbabilitySTKVDK CEEEEE 54.6 7.3 226.6 17.814795 7.7075e−70 1.00000 N 0.2409530.032161 TKVDKK EEEEEE 65.1 11.0 336.5 16.615803 3.4212e−61 1.00000 N0.193462 0.032601 SSTKVD HCEEEE 37.4 6.3 196.6 12.532954 3.0773e−351.00000 N 0.190234 0.032272 GSGKST CCCHHH 17.9 0.2 43.8 38.3507522.9572e−29 1.00000 B 0.408676 0.004880 TQTGKT CCCCHH 15.3 0.2 14.332.174467 1.3214e−26 1.00000 B 1.069930 0.013626 SAGIGR CCCCCH 7.5 0.014.7 117.545793 3.3253e−22 1.00000 B 0.510204 0.000277 VACKNG ECCCCC20.6 1.0 43.0 19.828434 5.1410e−22 1.00000 B 0.479070 0.023263 YASGRTHHCCCC 17.3 0.6 30.0 22.109277 5.3354e−22 1.00000 B 0.576667 0.019434SAGVGR CCCCHH 7.3 0.0 18.1 109.112108 1.3092e−21 1.00000 B 0.4033150.000247 DNAGKT CCCCHH 9.3 0.0 12.9 47.146776 8.7394e−21 1.00000 B0.720930 0.003000 NAGKTT CCCHHH 9.3 0.0 13.9 46.853654 1.4104e−201.00000 B 0.669065 0.002819 CSAGIG CCCCCC 6.3 0.0 11.9 123.1564466.8159e−20 1.00000 B 0.529412 0.000220 GVGKSA CCCHHH 12.4 0.2 44.028.043320 4.8288e−19 1.00000 B 0.281818 0.004327 TGTGKT CCCCHH 12.0 0.219.8 24.719102 5.6749e−19 1.00000 B 0.606061 0.011586 AAGKTT CCCHHH 9.00.1 18.0 37.604373 1.4562e−18 1.00000 B 0.500000 0.003152 DAAGKT CCCCHH9.0 0.1 18.0 35.241267 4.6128e−18 1.00000 B 0.500000 0.003584 CLGNICECCCCC 6.0 0.0 9.0 78.058006 6.6601e−18 1.00000 B 0.666667 0.000656GTDVVG CCCHHH 2.0 0.0 2.0 11.083550 7.0003e−18 1.00000 B 1.0000000.016020 PTVVNIG CEECCC 12.3 0.1 9.3 26.586731 1.6109e−17 1.00000 B1.322581 0.012986 CSAGVG CCCCCH 5.8 0.0 16.0 124.248581 4.0798e−171.00000 B 0.362500 0.000136 HIASVA EEEECC 3.0 0.0 1.0 5.5920421.0758e−16 1.00000 B 3.000000 0.030988 ALASTA CCCCCC 1.0 0.0 1.06.347379 1.0833e−16 1.00000 B 1.000000 0.024219 GTMKPV CCCCCE 1.7 0.01.0 6.517403 1.0847e−16 1.00000 B 1.700000 0.023001 AEKGLV HHHCCC 1.00.0 1.0 6.758211 1.0864e−16 1.00000 B 1.000000 0.021425 ANALAS CCCCCC1.0 0.0 1.0 7.841519 1.0925e−16 1.00000 B 1.000000 0.016003 YIKIHAEECCCC 1.5 0.0 1.0 7.920066 1.0928e−16 1.00000 B 1.500000 0.015692RITTLD EEEEEE 1.0 0.0 1.0 8.134587 1.0937e−16 1.00000 B 1.0000000.014887 NALAST CCCCCC 1.0 0.0 1.0 8.915828 1.0964e−16 1.00000 B1.000000 0.012424 RSLFLE CCCHHH 1.0 0.0 1.0 10.050382 1.0993e−16 1.00000B 1.000000 0.009803 GYRDNG CCEEEE 1.0 0.0 1.0 18.161797 1.1069e−161.00000 B 1.000000 0.003023 GSGKTT CCCHHH 11.2 0.2 31.1 22.1915574.5690e−16 1.00000 B 0.360129 0.007897 SAGIGR CCCCHH 5.9 0.0 20.088.105700 8.7484e−16 1.00000 B 0.295000 0.000224 DGGTGK CCCCCH 8.0 0.129.0 32.442436 1.3906e−15 1.00000 B 0.275862 0.002070 LDNAGK CCCCCH 6.30.0 10.5 52.016926 1.6033e−15 1.00000 B 0.600000 0.001392 GTGKTF CCCHHH8.0 0.1 9.8 26.155884 2.0446e−15 1.00000 B 0.816327 0.009416 NTKVDKCEEEEE 28.8 4.5 135.4 11.725183 2.2882e−15 1.00000 B 0.212703 0.032917SGVGKS CCCCHH 11.3 0.3 32.4 20.191824 3.7718e−15 1.00000 B 0.3487650.009246 GAGKTT CCCHHH 9.0 0.1 16.9 23.668066 4.2461e−15 1.00000 B0.532544 0.008359 GVGKSS CCCHHH 8.0 0.1 18.0 27.100944 1.1064e−141.00000 B 0.444444 0.004761 ACNGDS CCCCCC 5.0 0.0 6.0 58.0639601.7133e−14 1.00000 B 0.833333 0.001234 IVNYTP ECCCCC 9.3 0.2 22.021.034466 8.1515e−14 1.00000 B 0.422727 0.008602 MELCTL EECCCC 7.0 0.19.1 25.425349 1.0255e−13 1.00000 B 0.769231 0.008220 CSAGIG CCCCCH 4.50.0 9.7 105.776723 1.0959e−13 1.00000 B 0.463918 0.000186 LGNICR CCCCCH4.0 0.0 7.8 98.011647 1.2752e−13 1.00000 B 0.512821 0.000213 QTGTGKCCCCCH 7.5 0.1 10.0 25.450191 1.9828e−13 1.00000 B 0.750000 0.008561GVGKSN CCCHHH 6.3 0.0 11.0 31.334402 7.4332e−13 1.00000 B 0.5727270.003642 GQGIMS CCCHHH 5.0 0.0 5.0 36.328434 7.6590e−13 1.00000 B1.000000 0.003774 SSTGNT CCCCHH 7.0 0.1 6.0 22.498314 2.5846e−12 1.00000B 1.166667 0.011715 NVACKN EECCCC 13.3 0.9 43.0 12.867025 3.8275e−121.00000 B 0.309302 0.021930 RIVNYT EECCCC 8.8 0.2 22.1 18.8918053.9882e−12 1.00000 B 0.398190 0.009447 DSGVGK CCCCCH 8.3 0.2 35.519.948620 4.0221e−12 1.00000 B 0.233803 0.004704 QGSGKT CCCCHH 6.2 0.112.0 27.121341 4.5823e−12 1.00000 B 0.516667 0.004301 PNGSGK CCCCCH 5.00.0 10.1 37.000198 5.0129e−12 1.00000 B 0.495050 0.001798 GGTGKT CCCCHH8.0 0.2 30.9 19.161996 5.2279e−12 1.00000 B 0.258900 0.005436 KNVACKEEECCC 13.7 1.1 42.0 12.473295 6.8302e−12 1.00000 B 0.326190 0.025102GAGKTS CCCHHH 4.6 0.0 6.0 57.795480 7.3969e−12 1.00000 B 0.7666670.001054 NQTPNR HHCHHH 12.8 0.9 46.4 12.726660 1.4674e−11 1.00000 B0.275862 0.019236 VDHGKT CCCCHH 6.5 0.1 27.3 25.428433 2.6010e−111.00000 B 0.238095 0.002352 QALSGL HHHHHH 3.0 0.0 5.0 109.1145493.4511e−11 1.00000 B 0.600000 0.000151 VSWGRG EEECCC 4.3 0.0 5.344.147984 5.1163e−11 1.00000 B 0.811321 0.001785 SGSGKS CCCCHH 6.7 0.119.8 22.942534 5.9262e−11 1.00000 B 0.338384 0.004218 NSGKTT CCCHHH 6.50.1 9.0 20.353985 7.7073e−11 1.00000 B 0.722222 0.011109 GVGKTS CCCHHH6.0 0.1 20.1 21.831417 9.5206e−11 1.00000 B 0.298507 0.003679 DHGKTTCCCHHH 6.0 0.1 28.2 20.841979 2.0824e−10 1.00000 B 0.212766 0.002868LNVGMV CEEEEE 3.3 0.0 5.0 83.763342 2.0891e−10 1.00000 B 0.6600000.000310 QCGSCW CCCCHH 4.4 0.0 20.2 40.547665 3.4174e−10 1.00000 B0.217822 0.000580 PSGSGK CCCCCH 4.0 0.0 8.0 35.524057 4.3113e−10 1.00000B 0.500000 0.001577 GGVGKS CCCCHH 9.1 0.5 53.2 12.788361 8.0126e−101.00000 B 0.171053 0.008654 GTGKTT CCCHHH 8.0 0.3 45.2 13.8270639.0377e−10 1.00000 B 0.176991 0.006888 GSTVEK CEEEEE 10.5 0.8 24.411.145641 9.7627e−10 1.00000 B 0.430328 0.032173 LSGAGK CCCCCH 4.0 0.04.9 28.128509 1.2381e−09 1.00000 B 0.816327 0.004102 EFTFPD CCCCCC 8.60.5 14.0 12.223542 1.3797e−09 1.00000 B 0.614286 0.032760 VEFTFP CCCCCC8.6 0.5 14.0 12.179844 1.4535e−09 1.00000 B 0.614286 0.032978 GLGFSIECCEEE 4.0 0.0 4.4 26.233665 1.5884e−09 1.00000 B 0.909091 0.005251NGSGKS CCCCHH 5.0 0.1 13.1 21.272338 1.6003e−09 1.00000 B 0.3816790.004143 SWGRGC EECCCC 4.3 0.0 5.3 28.630970 1.6081e−09 1.00000 B0.811321 0.004230 QGQGIM CCCCHH 4.8 0.0 5.0 26.582255 1.7583e−09 1.00000B 0.960000 0.006475 KCKACH HCCCCC 5.0 0.1 5.1 16.352193 2.3466e−091.00000 B 0.980392 0.017989 AAGKST CCCHHH 4.1 0.0 6.0 26.9347732.8975e−09 1.00000 B 0.683333 0.003833 NVGKST CCCHHH 6.0 0.1 18.015.762169 3.6864e−09 1.00000 B 0.333333 0.007740 PNVGKS CCCCHH 6.0 0.119.0 15.593755 4.3819e−09 1.00000 B 0.315789 0.007483 WGHGYA CCCCHH 5.00.0 4.0 21.902956 4.6751e−09 1.00000 B 1.250000 0.008269 GHGYAT CCCHHH5.0 0.0 4.0 20.616189 7.5561e−09 1.00000 B 1.250000 0.009323 RVEFTFCCCCCC 6.9 0.3 9.0 12.256272 1.1956e−08 1.00000 B 0.766667 0.033331ELGPLR CCCCCE 5.7 0.1 6.0 15.016070 1.2482e−08 1.00000 B 0.9500000.023394 GTGKSC CCCHHH 4.0 0.0 5.1 20.988541 1.3877e−08 1.00000 B0.784314 0.007044 STGAGK CCCCCH 4.6 0.0 7.1 23.047849 1.4152e−08 1.00000B 0.647887 0.005546 QRRGLG CCCCHH 5.0 0.1 6.0 14.511493 1.5619e−081.00000 B 0.833333 0.019253 INGNSA HHCCHH 5.0 0.1 5.0 13.1724051.7239e−08 1.00000 B 1.000000 0.028009 STVEKT EEEEEE 9.5 0.8 24.410.028684 1.8503e−08 1.00000 B 0.389344 0.032003 TLKGET CCEEEE 6.0 0.29.0 12.310119 1.9569e−08 1.00000 B 0.666667 0.025076 PLRSFK CCEEEE 5.40.1 5.7 13.898421 2.5175e−08 1.00000 B 0.947368 0.025727 GLTDWK EECCCC5.2 0.1 9.4 15.570150 2.6117e−08 1.00000 B 0.553191 0.011510 PGSGKGCCCCHH 5.0 0.1 10.1 15.466402 2.6172e−08 1.00000 B 0.495050 0.010033GPLRSF CCCEEE 5.5 0.2 5.8 13.909240 2.6726e−08 1.00000 B 0.9482760.026176 SPSSLS ECCEEE 15.8 2.7 85.6 8.005725 2.9307e−08 1.00000 B0.184579 0.032087 LGPLRS CCCCEE 5.7 0.2 6.0 13.596746 3.2676e−08 1.00000B 0.950000 0.028372 PSSLSA CCEEEE 13.1 1.8 90.4 8.382019 3.8044e−081.00000 B 0.144912 0.020372 SVGKTS CCCHHH 4.0 0.0 10.0 20.3581524.3082e−08 1.00000 B 0.400000 0.003802

TABLE 36 (Table 36, in its entirety, discloses SEQ ID NOS 3,187-5,226,respectively, in order of appearance) Num In Ex- Null Num Num Chain-Non- Epi- pected In P-Value Observed Prob- Crystal Interface sets WaterSequence Structure topes In Epi PDB Z-Score Upper Ratio ability SetsIntersets 25 Solvent FxGHxA CcCHhH 10.6 0.1 13 40.14033 2.0626e−210.815385 0.005323 11 6 1 0.021 FPGHxA CCCHhH 10.6 0.1 13 38.74964.1480e−21 0.815385 0.005708 11 6 1 0.021 FPxHxA CCcHhH 11.6 0.1 14.236.45081 4.1020e−22 0.816901 0.007059 12 6 1 0.021 ExxxMD HhhhEC 16.70.2 36.2 35.39318 6.7544e−27 0.461326 0.006027 17 8 1 5.181 FPGH CCCH11.5 0.2 16.2 28.66959 1.9821e−19 0.709877 0.009756 11 6 1 0.021 FxxHxACccHhH 11.6 0.2 19 27.92433 7.9156e−19 0.610526 0.008899 12 6 1 0.021ERxxMD HHhhEC 15.1 0.2 36.2 30.59899 8.7736e−24 0.417127 0.00656 17 8 15.134 LGxSI CCeEE 12.5 0.2 38.3 25.47832 3.4342e−18 0.326371 0.006089 1213 8 5 FxGH CcCH 12.2 0.2 23.1 25.02609 1.0525e−18 0.528139 0.010002 127 2 0.021 PxHxAL CcHhHC 11 0.3 13.1 20.59324 3.3394e−17 0.8396950.021144 11 5 1 0 PGHxxL CCHhhC 11.7 0.3 13 21.21613 1.9065e−17 0.90.022743 11 5 1 0 RxxMDS HhhECC 16.7 0.4 42.2 24.91901 6.1180e−220.395735 0.010205 18 10 1 5.157 RxxMD HhhEC 17.1 0.6 44.2 22.23852.7644e−21 0.386878 0.012675 19 10 1 5.157 KxxFTV HhcCCH 11.1 0.4 14.117.68718 1.7765e−15 0.787234 0.026782 12 7 7 0 KxxFxV HhcCcH 11.6 0.415.8 17.89308 3.6601e−15 0.734177 0.025436 13 8 8 0 FPGxxA CCChhH 11.60.4 23 17.67412 2.5125e−14 0.504348 0.017749 11 6 1 0.021 NYTxxL CCCccC10.1 0.4 33 16.31284 1.6032e−12 0.306061 0.010921 11 2 1 1.5 VACxxGECCccC 33.4 1.2 47.1 29.57423 6.3139e−42 0.70913 0.025811 29 15 1 5.755PxHxxL CcHhhC 12.9 0.5 18.3 18.1817 2.5192e−16 0.704918 0.026188 12 5 10 FPxH CCcH 12.5 0.5 22.2 17.81482 2.2978e−15 0.563063 0.020995 12 6 10.021 LxxNVM CchHHH 18.1 0.7 30.9 20.92111 3.8340e−22 0.585761 0.02289118 12 1 1.542 VACKxG ECCCcC 31.1 1.2 45 27.21317 4.3643e−38 0.6911110.027516 27 13 1 5.505 NYTPxL CCCCcC 10.1 0.4 32 15.30607 4.9076e−120.315625 0.012696 11 2 1 1.5 CKxGxT CCcCcC 27.2 1.1 50 25.153549.5225e−32 0.544 0.022017 26 14 1 5.231 VxCxxG EcCccC 40.5 1.7 79.330.25631 1.7042e−45 0.510719 0.021207 37 19 1 8.755 PGHxA CCHhH 11.3 0.518.8 15.37671 2.0088e−13 0.601064 0.026934 12 7 2 0.688 VACxNG ECCcCC21.6 1 44 21.15107 8.7514e−24 0.490909 0.022104 19 13 1 4.438 VxCKxGEcCCcC 37.2 1.7 58.6 27.64679 3.2831e−42 0.634812 0.028979 34 16 1 8.505MDSS ECCC 14.9 0.7 43.2 17.35742 4.1795e−16 0.344907 0.015781 15 10 25.204 VxCxNG EcCcCC 27.6 1.3 56.3 22.96562 2.7459e−29 0.490231 0.0237925 15 1 7.438 VACKNG ECCCCC 20.6 1 43 19.82843 5.1410e−22 0.479070.023263 18 12 1 4.438 NxTPxL CcCCcC 11.8 0.6 39.8 14.91701 1.9147e−120.296482 0.014437 13 4 3 3.334 GFTxS CCHhH 25.7 1.3 42.2 21.824777.8086e−28 0.609005 0.030577 24 15 1 4.165 IVNYxP ECCCcC 10.3 0.5 2213.76618 1.8207e−11 0.468182 0.023508 12 2 1 1.375 GFxNS CChHH 25.7 1.343.2 21.48449 2.0443e−27 0.594907 0.030734 24 15 1 4.171 GFTNS CCHHH24.7 1.3 41.2 20.89447 2.9243e−26 0.599515 0.031442 23 14 1 4.165 VxCKNGEcCCCC 26.6 1.4 55.2 21.38084 4.0094e−27 0.481884 0.025784 24 14 1 7.438IVxYxP ECcCcC 10.3 0.6 23 13.2175 4.2034e−11 0.447826 0.024211 12 2 11.375 IVNxxP ECCccC 10.3 0.6 22 13.08393 4.5307e−11 0.468182 0.025815 122 1 1.375 LxxNxM CchHhH 18.1 1 44.6 17.17364 1.8356e−18 0.40583 0.02271218 12 1 1.542 GHxxL CHhhC 13.2 0.8 17.8 14.59737 6.8060e−15 0.7415730.042626 12 7 2 0 LxxxVM CchhHH 23.7 1.4 59.7 19.2235 6.7876e−230.396985 0.023116 22 14 2 1.542 ACKxG CCCcC 34.1 2 46.4 23.183661.3729e−36 0.734914 0.043173 29 16 1 6.755 GxTNS CcHHH 24.7 1.5 42.719.6171 6.3209e−25 0.578454 0.034045 23 14 1 4.165 RIxxNL HHhhHH 16.5 144 15.84119 4.4922e−16 0.375 0.022308 17 5 2 5.708 NxGYH EcCCE 11.7 0.737.8 13.20822 2.2537e−11 0.309524 0.018678 13 7 1 4.817 VACxN ECCcC 21.91.3 45 18.01829 2.2608e−21 0.486667 0.029818 20 14 1 5.188 PSVY CEEE17.5 1.1 268.7 15.82354 1.2792e−15 0.065128 0.004023 23 13 1 3.071CxNGxT CcCCcC 19 1.2 51.6 16.57241 2.1832e−18 0.368217 0.022926 19 15 14.652 CKNGxT CCCCcC 16.8 1.1 47.2 15.53404 7.2121e−16 0.355932 0.02227216 12 1 3.438 FTxxxN CChhhH 10 0.6 19.8 12.03098 1.2267e−10 0.5050510.031658 10 6 6 1 NxQxQF CcCcCE 10.1 0.6 29.2 11.9082 3.6689e−10 0.345890.022079 11 11 1 1 QFxTN CEcCC 17.3 1.1 28.1 15.7038 1.4457e−17 0.6156580.039391 13 15 1 6 NxxYH EccCE 11.7 0.8 37.8 12.74759 4.4345e−110.309524 0.019907 13 7 1 4.817 ERxxxD HHhheC 16.2 1 36.2 15.054078.6591e−16 0.447514 0.028832 18 9 1 6.134 LxxKDY HhhCCC 12.4 0.8 17.513.25842 4.4705e−13 0.708571 0.045827 11 5 2 0.333 QFNTN CECCC 16.8 1.128.1 15.36943 1.1857e−16 0.597865 0.038692 12 14 1 6 NVACK EECCC 24.21.6 45 18.28235 1.9905e−23 0.537778 0.035242 23 10 1 5.523 PGxxAL CChhHC10.3 0.7 15.5 11.89251 7.8512e−11 0.664516 0.044128 10 5 1 0 VxCKN EcCCC27.9 1.9 55.4 19.44521 3.8832e−26 0.50361 0.033503 26 16 1 8.188 NVACxNEECCcC 14.3 1 43.1 13.79284 2.2413e−13 0.331787 0.022206 14 10 1 4.392CKNxxT CCCccC 16.8 1.2 47.7 14.76365 3.0318e−15 0.352201 0.024136 16 121 3.438 NxTPNR HhCHHH 13.8 1 46.4 13.28837 1.7188e−12 0.297414 0.02056314 10 1 3.816 VAxKxG ECcCcC 31.1 2.2 50.4 20.1751 6.0519e−30 0.6170630.042673 27 13 1 5.505 VACKN ECCCC 20.9 1.5 43 16.41255 2.2938e−190.486047 0.033792 19 13 1 5.188 GYSxxN CEChhH 13 0.9 42.3 12.842953.1635e−12 0.307329 0.021422 15 15 1 3.062 GFxxxG CEeeeE 11.7 0.8 72.612.12061 2.1618e−10 0.161157 0.011234 12 13 6 3.5 NQTPNR HHCHHH 12.8 0.946.4 12.72666 1.4674e−11 0.275862 0.019236 13 9 1 3.816 YSxMS CCcEE 11.70.8 42.8 12.16388 1.2625e−10 0.273364 0.019069 15 14 1 3.966 KxYRxECcCCcC 11.8 0.8 21.3 12.33046 1.9943e−11 0.553991 0.038696 10 4 2 0.333NxACK EeCCC 24.2 1.7 45 17.62335 9.2961e−23 0.537778 0.037658 23 10 15.523 NQTxNR HHChHH 12.8 0.9 46.4 12.69165 1.5524e−11 0.275862 0.0193313 9 1 3.816 NVxCK EEcCC 24.2 1.7 45 17.59016 1.0058e−22 0.5377780.037786 23 10 1 5.523 YTPxL CCCcC 11.1 0.8 39.8 11.76239 2.0298e−100.278894 0.019713 12 3 1 1.5 NVAC EECC 26.5 1.9 49.4 18.34496 1.9069e−240.536437 0.037918 25 12 1 5.773 NVACKN EECCCC 13.3 0.9 43 12.867033.8275e−12 0.309302 0.02193 13 9 1 4.392 QFNxN CECcC 17.1 1.2 28.114.7482 8.3663e−17 0.608541 0.043159 12 14 1 6 FTVA CCHH 13.1 0.9 19.612.93532 2.1141e−13 0.668367 0.047415 14 8 7 0 VxCxN EcCcC 28.9 2.1 67.319.01138 1.1251e−25 0.429421 0.030557 27 17 1 8.188 YSTMS CCCEE 11.7 0.842.8 12.01448 1.5892e−10 0.273364 0.01949 15 14 1 3.966 PPGPP CCCCC 16.81.2 31 14.51712 1.0146e−15 0.541935 0.038746 2 17 2 0 NxTxNR HhChHH 13.81 47.4 13.0352 2.7237e−12 0.291139 0.020818 14 10 1 3.816 ERxxM HHhhE17.3 1.2 36.5 14.66555 4.8047e−16 0.473973 0.034006 18 9 1 5.134 GxGFEcCE 16.8 1.2 40.5 14.39904 3.7361e−15 0.414815 0.029841 16 18 9 7.666NVxCxN EEcCcC 14.3 1 43.1 13.21465 6.2025e−13 0.331787 0.023961 14 10 14.392 YxTMS CcCEE 11.7 0.8 42.8 11.91659 1.8497e−10 0.273364 0.019773 1514 1 3.966 GFxxS CChhH 27 2 67.8 18.15516 5.3814e−24 0.39823 0.028894 2618 2 4.171 VACK ECCC 33.2 2.4 45 20.37365 1.4230e−32 0.737778 0.05361930 14 1 6.435 VxCK EcCC 42 3.1 60.9 22.84323 2.8454e−40 0.6896550.050241 40 20 1 9.435 NxAC EeCC 27 2 50.4 18.15349 6.3631e−25 0.5357140.039237 25 12 1 5.773 NxTPxR HhCHhH 13.9 1 46.4 12.9093 2.3592e−120.299569 0.021942 14 10 1 3.829 SxMS CcEE 14.9 1.1 51.5 13.353273.9684e−13 0.28932 0.021211 17 17 1 4.466 STMS CCEE 14.9 1.1 42.813.37733 2.6426e−13 0.348131 0.025541 17 17 1 4.466 NVxC EEcC 26.5 1.952.2 17.92263 8.5115e−24 0.507663 0.037341 25 12 1 5.773 NxACxN EeCCcC14.3 1.1 43 12.98435 9.3387e−13 0.332558 0.024775 14 10 1 4.392 QFxTCEcC 21.3 1.6 29.7 16.06162 9.1250e−21 0.717172 0.053568 17 19 2 7TVAxxE CHHhhH 14.8 1.1 24.2 13.27204 6.4829e−14 0.61157 0.046058 15 9 81 NQTPxR HHCHhH 12.9 1 46.4 12.19015 2.5665e−11 0.278017 0.02106 13 9 13.829 TMxRI HHhHH 11.4 0.9 25.5 11.525 1.5721e−10 0.447059 0.033919 14 41 3.146 YxxMS CccEE 11.7 0.9 44.7 11.58861 3.2547e−10 0.261745 0.01986815 14 1 3.966 ACxNG CCcCC 22.7 1.7 46.9 16.27224 5.2201e−20 0.4840090.03678 20 15 2 4.549 ACKNG CCCCC 21.6 1.7 43 15.80433 3.8946e−190.502326 0.038517 18 13 1 4.438 KxVxCK EeEcCC 17.6 1.4 47.7 14.183373.3780e−15 0.368973 0.028318 19 10 1 2.55 KxVAC EeECC 17.6 1.4 4214.19049 2.2162e−15 0.419048 0.032245 19 12 1 2.8 KNVACK EEECCC 13.7 1.142 12.4733 6.8302e−12 0.32619 0.025102 15 9 1 2.431 RxxMxS HhhEcC 16.71.3 42.2 13.80189 1.5849e−14 0.395735 0.030483 18 10 1 5.157 KxVACKEeECCC 15.3 1.2 42 13.18095 1.8560e−13 0.364286 0.028111 16 9 1 2.55NQTxxR HHChhH 12.9 1 46.4 12.05315 3.2314e−11 0.278017 0.021481 13 9 13.829 KNxAC EEeCC 16.4 1.3 42 13.64298 2.3347e−14 0.390476 0.030201 1812 1 2.681 NxTxxR HhChhH 13.9 1.1 47.4 12.49716 5.0108e−12 0.2932490.022727 14 10 1 3.829 FxTxxR ChHhhH 13.6 1.1 20.2 12.53096 6.0951e−130.673267 0.052338 13 7 1 2.833 GYxxxN CEchhH 14 1.1 42.3 12.536421.6774e−12 0.330969 0.025738 16 16 1 3.062 NVxCKN EEcCCC 13.3 1 4312.19847 1.2220e−11 0.309302 0.024087 13 9 1 4.392 KNVAC EEECC 15.9 1.242.1 13.36749 7.6225e−14 0.377672 0.029438 18 12 1 2.681 NxxCxN EecCcC14.5 1.1 43 12.72668 1.5589e−12 0.337209 0.026349 14 11 1 4.438 KNxxCEEecC 16.4 1.3 42 13.54722 2.8206e−14 0.390476 0.030577 18 12 1 2.681KNVxC EEEcC 15.9 1.2 42.1 13.32532 8.2636e−14 0.377672 0.029601 18 12 12.681 WCxP CChH 33.3 2.6 62.5 19.37311 4.2055e−29 0.5328 0.041887 35 4017 8.539 QFNT CECC 19.8 1.6 28.2 15.03871 1.4634e−18 0.702128 0.05523 1517 1 7 KNVxCK EEEcCC 13.7 1.1 42 12.27342 9.7008e−12 0.32619 0.025822 159 1 2.431 VAxKNG ECcCCC 20.6 1.6 43 15.11451 7.1138e−18 0.47907 0.03805718 12 1 4.438 FRxxD HHhhC 17.5 1.4 102.5 13.73082 3.4864e−14 0.1707320.013607 20 21 8 1.25 RxxLPE HhhCCC 11.6 0.9 30.6 11.27164 3.4023e−100.379085 0.030226 12 7 6 2.06 FTxS CHhH 27.7 2.2 52.5 17.490096.0171e−24 0.527619 0.042219 26 17 2 4.171 FTNS CHHH 25.7 2.1 47.216.82928 2.2403e−22 0.544492 0.043704 24 15 1 4.171 FxGxxA CcChhH 13.11.1 51 11.86862 2.5395e−11 0.256863 0.02063 13 8 3 0.021 NxACKN EeCCCC13.3 1.1 43 11.98009 1.8020e−11 0.309302 0.024858 13 9 1 4.392 QTxxAKHHhhHH 11.5 0.9 25.1 11.04198 3.3849e−10 0.458167 0.037806 8 10 4 2SxKPxY CcCCcC 12.3 1 23.8 11.4035 4.1050e−11 0.516807 0.042941 12 11 30.511 TxxLxK CccCcH 12.8 1.1 41.4 11.51471 9.3815e−11 0.309179 0.02574715 7 6 2 VAC ECC 35.5 3 69.4 19.30368 1.0904e−29 0.511527 0.042754 32 161 6.685 ExxxxD HhhheC 18.8 1.6 44.9 13.98063 1.0075e−15 0.4187080.035042 19 10 2 6.181 KNxACK EEeCCC 13.7 1.1 42 11.87452 1.9766e−110.32619 0.027349 15 9 1 2.431 NxxCK EecCC 24.2 2 45 15.92761 6.0120e−210.537778 0.045091 23 10 1 5.523 NxxxQF CcccCE 17.8 1.5 51.1 13.545331.1983e−14 0.348337 0.029216 15 16 2 5 FxNS ChHH 27.7 2.3 55.4 16.958633.7819e−23 0.5 0.042157 26 17 2 4.176 QTPNR HCHHH 17.2 1.5 46.4 13.229392.0671e−14 0.37069 0.031495 18 13 1 5.816 GSTVE CEEEE 15.9 1.4 24.412.86514 2.1829e−14 0.651639 0.055473 17 10 1 1.048 ExxxM HhhhE 21 1.840.6 14.696 2.8903e−18 0.517241 0.044034 20 11 2 5.181 CExxxY EEcccC17.7 1.5 50.9 13.36287 2.0202e−14 0.347741 0.029713 18 13 1 8.785 STVExTEEEEeE 11.4 1 24.4 10.71527 5.4506e−10 0.467213 0.04035 12 4 1 1 NQxPNRHHcHHH 12.9 1.1 47.4 11.21815 1.4078e−10 0.272152 0.023798 13 9 1 3.818MxxSRN HhhHCC 13.4 1.2 42 11.44511 4.7252e−11 0.319048 0.027951 16 6 11.311 QTPxR HCHhH 17.2 1.5 46.4 12.98164 3.4999e−14 0.37069 0.032542 1813 1 5.829 QTxNR HChHH 17.2 1.5 46.4 12.93232 3.8897e−14 0.370690.032756 18 13 1 5.816 KNxxCK EEecCC 13.7 1.2 42 11.50467 3.8780e−110.32619 0.028883 15 9 1 2.431 QFxxN CEccC 17.6 1.6 32.4 13.170196.2448e−15 0.54321 0.048103 13 15 1 6 NxxCKN EecCCC 13.3 1.2 43 11.287296.3736e−11 0.309302 0.027552 13 9 1 4.392 GxTxS CcHhH 25.7 2.3 77.115.70055 6.1084e−20 0.333333 0.029715 24 15 1 4.165 WCGP CCHH 23.2 2.148.1 14.99016 3.7261e−19 0.482328 0.043149 23 26 10 4.472 GxGxxI EcCeeE12.5 1.1 47.7 10.87978 4.3984e−10 0.262055 0.023487 15 20 10 3.741NxxPNR HhcHHH 13.9 1.2 47.4 11.48023 3.1658e−11 0.293249 0.026318 14 101 3.821 LxxSI CceEE 12.8 1.2 68.5 10.91686 4.6230e−10 0.186861 0.0168913 14 9 5.25 DxPExL EhHHhH 12.7 1.2 38 10.91795 2.7228e−10 0.3342110.030355 14 6 1 1 GxSxxN CeChhH 21.5 2 57.9 14.18641 6.8792e−17 0.371330.033905 24 20 1 3.231 CxxGxT CccCcC 36.2 3.3 126.6 18.27505 5.0452e−270.28594 0.026253 34 24 6 8.695 TLIS EEEE 13.7 1.3 44.6 11.229347.1321e−11 0.307175 0.028307 15 1 1 1.601 FPExLT HHHhHH 14.2 1.3 57.911.37831 2.9795e−11 0.24525 0.02267 16 4 1 2 DxQAxC HhHHhH 12 1.1 49.110.41466 8.3369e−10 0.244399 0.022756 14 4 1 2.023 KxxACK EeeCCC 15.31.4 42 11.76957 3.0198e−12 0.364286 0.034205 16 9 1 2.55 LSxxYH HHhhHH26.5 2.5 52.5 15.58336 4.0718e−21 0.504762 0.047463 26 29 7 6.747 CKNGCCCC 32.8 3.1 60.3 17.22489 5.4973e−26 0.543947 0.0519 30 21 2 7.606KxVxC EeEcC 19.9 1.9 57.7 13.26771 2.7457e−15 0.344887 0.032977 22 13 12.8 PxHxA CcHhH 13.8 1.3 42.8 11.02507 8.4644e−11 0.32243 0.030883 16 94 0.688 QTxxR HChhH 18.2 1.8 48.4 12.64218 2.9192e−14 0.376033 0.03627419 14 2 5.829 KxxxCK EeecCC 17.6 1.7 48.7 12.38274 1.5752e−13 0.3613960.035054 19 10 1 2.55 SRW CHH 21.5 2.1 52.8 13.57701 2.1455e−16 0.4071970.040196 23 13 1 2.333 PxxxAL CchhHC 12.4 1.2 28.2 10.32078 4.9428e−100.439716 0.043459 12 6 2 0 NQxPxR HHcHhH 12.9 1.3 49.2 10.416786.2879e−10 0.262195 0.025975 13 9 1 3.831 KxxAC EeeCC 18.1 1.8 4412.34444 3.9683e−14 0.411364 0.041254 19 12 1 2.8 KSRW CCHH 15.6 1.645.6 11.35132 8.7811e−12 0.342105 0.034653 18 10 1 2.333 DKPxY CCCcC13.2 1.3 21.2 10.59411 3.0412e−11 0.622642 0.063119 12 15 2 0.154 QxPNRHcHHH 17.2 1.8 47.4 11.86389 4.3286e−13 0.362869 0.037114 18 13 1 5.818RIxxxQ CCchhH 14.1 1.5 60.7 10.62227 1.3315e−10 0.23229 0.023928 14 1410 4.532 TMS CEE 18 1.9 61.6 11.97645 2.1832e−13 0.292208 0.030366 20 202 4.966 FNTN ECCC 18.2 1.9 37.6 12.12908 3.7927e−14 0.484043 0.05058 1315 2 6 ACKN CCCC 22.1 2.3 44 13.35197 4.5720e−17 0.502273 0.052665 19 141 5.938 SxYQxE ChHHhH 14.9 1.6 34.9 10.89402 1.9565e−11 0.4269340.044931 12 17 2 0.035 QxNTN CeCCC 17.4 1.8 28.1 11.88416 5.1239e−140.619217 0.065309 12 14 1 6 CxNxxT CcCccC 21.3 2.3 79.4 12.866024.0656e−15 0.268262 0.028403 20 16 2 5.815 RxxxDS HhheCC 16.7 1.8 45.211.42834 2.6297e−12 0.369469 0.039275 18 10 1 5.157 YSTM CCCE 19.6 2.142.7 12.43726 1.1609e−14 0.459016 0.04883 21 21 1 4.292 MxxSxN HhhHcC14.4 1.5 54.6 10.54436 1.5677e−10 0.263736 0.028063 17 7 2 3.311 KPLYCCCC 17.3 1.9 20.1 11.92052 1.7658e−15 0.860697 0.092045 13 18 1 0.511VxxKNG EccCCC 26.6 2.8 57.3 14.43446 1.7747e−19 0.464223 0.049723 24 141 7.438 LxxKxY HhhCcC 22.3 2.4 89.2 13.02413 1.5264e−15 0.25 0.026898 1812 7 0.583 YxTM CcCE 19.6 2.1 43.7 12.25205 2.0037e−14 0.448513 0.04888221 21 1 4.292 GSTxE CEEeE 15.9 1.8 28 10.9919 2.4901e−12 0.5678570.063033 17 10 1 1.048 LxSxxR CcHhhH 20 2.2 79.5 12.06154 5.7006e−140.251572 0.028083 23 23 17 0.003 KDYR CCCC 12.5 1.4 21 9.7140236.6677e−10 0.595238 0.066625 12 8 4 0.333 VAxxNG ECccCC 21.6 2.4 46.612.56938 1.5977e−15 0.463519 0.052575 19 13 1 4.438 NVAxK EECcC 24.2 2.748.5 13.32393 1.1195e−17 0.498969 0.056658 23 10 1 5.523 YSxM CCcE 23.72.8 61.6 12.84049 3.5944e−16 0.38474 0.045127 25 24 2 5.861 TPNR CHHH 222.6 54.2 12.38537 1.5783e−15 0.405904 0.047623 22 17 1 9.316 GxxNS CchHH25.9 3.1 66.8 13.3476 1.3878e−17 0.387725 0.045915 25 16 2 4.171 FPExxTHHHhhH 14.2 1.7 58.9 9.754512 8.2132e−10 0.241087 0.028739 16 4 1 2DxRExG EeEEcC 14.2 1.7 48 9.784977 5.8536e−10 0.295833 0.035279 14 6 11.307 YHxxNE HHhhHH 19.5 2.4 46.3 11.42206 2.0039e−13 0.421166 0.05119720 20 7 6.268 SxYxxE ChHhhH 23.4 2.9 60.5 12.39716 1.2306e−15 0.3867770.047559 19 29 4 0.405 MNIF CCHH 20.6 2.5 41.1 11.69437 2.3532e−140.501217 0.061842 20 6 1 7.935 MDS ECC 25.5 3.2 83.9 12.7748 2.5660e−160.303933 0.037835 24 16 6 5.204 GSxVE CEeEE 15.9 2 34.1 10.186493.2680e−11 0.466276 0.058124 17 10 1 1.048 CKxxxT CCcccC 29.6 3.7 96.113.6757 1.2906e−18 0.308012 0.038755 30 17 4 6.006 NPTxxE CCChhH 24.1 387.4 12.31285 1.9262e−15 0.275744 0.0347 25 27 2 3.167 FxxxxQ EcchhH21.5 2.7 95.3 11.59038 1.5552e−13 0.225603 0.028396 18 21 10 3.038 MxxSRHhhHC 19.9 2.5 52.1 11.26099 2.7264e−13 0.381958 0.048106 24 12 3 2.21CGP CHH 24.5 3.1 61.6 12.50142 4.2984e−16 0.397727 0.050135 25 28 114.722 KETxxA CCChhH 18.8 2.4 45.1 10.94829 1.1586e−12 0.416851 0.05267521 22 9 3.218 YHxxN HHhhH 50.5 6.5 81.8 18.01263 3.0622e−71 0.6173590.07928 34 49 9 15.429 QDKEG HHHHC 23.5 3 53.3 12.12891 1.5706e−150.440901 0.056696 22 22 1 4.063 FPExL HHHhH 17.3 2.3 71.5 10.17225.1552e−11 0.241958 0.03158 19 8 2 5 QxPxR HcHhH 18.2 2.4 55.2 10.489337.0720e−12 0.32971 0.043075 20 15 3 5.831 PGPP CCCC 27.7 3.6 50.413.13769 1.2393e−18 0.549603 0.071817 6 23 5 0 STM CCE 24.9 3.3 5712.3273 3.1613e−16 0.436842 0.057314 26 26 2 4.792 SxxYH HhhHH 55.1 7.3104 18.27618 2.0986e−73 0.529808 0.070636 39 53 14 16.197 STKVDK CEEEEE54.6 7.3 226.6 17.8148 7.7075e−70 0.240953 0.032161 61 14 1 4.5 KxVAxKEeECcC 15.3 2 42 9.504713 4.1563e−10 0.364286 0.048679 16 9 1 2.55 VxxxQCehhH 15.7 2.1 22.7 9.821201 2.0057e−11 0.69163 0.092986 11 16 5 0.045LGxxI CCeeE 20.7 2.8 133.5 10.8505 2.8269e−12 0.155056 0.020856 21 22 126.667 VAxxxG ECcccC 36.9 5 129.3 14.59237 8.2210e−22 0.285383 0.03849432 20 3 5.755 MxxxxS EecceE 14.3 1.9 28.5 9.210245 6.8755e−10 0.5017540.067857 14 14 10 0.5 QxNxN CeCcC 17.6 2.4 31.2 10.22307 5.2458e−120.564103 0.07679 12 14 1 6 ETGxS ECCcC 17.6 2.4 62 10.0008 6.3892e−110.283871 0.038748 20 13 1 6.266 TxDxxR CcHhhH 16.8 2.3 45.8 9.817229.5154e−11 0.366812 0.050164 14 21 13 7.167 ExGSS EcCCC 15.6 2.1 549.395607 8.4001e−10 0.288889 0.039586 20 15 2 3.386 QxxNR HchHH 17.2 2.447.4 9.883211 4.7054e−11 0.362869 0.050001 18 13 1 5.818 PGxxxL CChhhC18.3 2.5 95.4 10.04912 5.2259e−11 0.191824 0.026518 20 12 4 1 QFN CEC 253.5 41.7 12.09169 4.5918e−17 0.59952 0.082983 18 21 3 7 NMxxxE CCchhH 273.8 79.7 12.25384 1.9659e−16 0.33877 0.047324 31 20 14 3.042 NxRGxSCeCCeC 15.2 2.1 44 9.190897 9.0030e−10 0.345455 0.048322 17 14 1 4.851WCG CCH 28.7 4 56.9 12.76874 3.8448e−18 0.504394 0.070649 27 30 12 5.694VAxKN ECcCC 20.9 2.9 46.7 10.8279 2.6347e−13 0.447537 0.062888 19 13 15.188 NQTPN HHCHH 17.4 2.5 46.3 9.80733 5.7989e−11 0.37581 0.052976 1712 1 5.818 NxGY EcCC 21.7 3.1 58.1 10.9411 2.7368e−13 0.373494 0.0527223 15 5 7.527 DxPE EhHH 16.3 2.3 38.5 9.514759 1.5307e−10 0.4233770.059793 19 11 2 2.167 QxNxQ EeCcC 19.3 2.7 36.1 10.43716 9.0830e−130.534626 0.075549 17 19 2 1 QDKxG HHHhC 27.2 3.9 57.3 12.295144.3110e−17 0.474695 0.067418 23 26 1 4.063 GFTN CCHH 28.4 4 44.312.70299 6.0926e−19 0.641084 0.091314 26 19 1 5.255 STVE EEEE 17 2.4 309.755365 1.1687e−11 0.566667 0.080927 19 12 2 1.048 QDxEG HHhHC 26 3.753.3 11.93412 1.7775e−16 0.487805 0.070194 22 24 1 5.063 LxxxYH HhhhHH29.3 4.2 149.9 12.33288 2.6305e−16 0.195464 0.028332 29 32 9 6.747 KSxWCChH 17.5 2.5 59.4 9.591293 1.6500e−10 0.294613 0.04278 20 12 3 3.333PxGPP CcCCC 18.4 2.7 56 9.854107 3.9241e−11 0.328571 0.047758 3 20 3 0NxAxK EeCcC 24.7 3.6 55.5 11.50343 4.7976e−15 0.445045 0.064834 24 11 25.523 MxIF CcHH 24.6 3.6 56.8 11.45787 6.4773e−15 0.433099 0.063193 2410 3 7.935 GxLxL CcCcH 18.9 2.8 110.4 9.756476 8.9145e−11 0.1711960.025321 17 19 16 0.071 GxTVE CeEEE 19.5 2.9 45.9 10.09136 6.2818e−120.424837 0.062984 21 12 2 1.048 ACxxG CCccC 42.2 6.3 122.4 14.733493.9997e−48 0.344771 0.051214 35 26 5 7.116 NxxGxS CecCeC 18.6 2.8 49.79.784163 3.5481e−11 0.374245 0.055768 20 17 2 4.851 ExxLxY HhhHhC 17 2.569.1 9.239619 4.0465e−10 0.24602 0.036788 23 21 13 6.077 QxQxN CcCeC16.7 2.5 32.4 9.345434 1.2978e−10 0.515432 0.077204 16 17 2 2 TxNR ChHH29 4.4 76.1 12.1332 6.1385e−17 0.381078 0.057443 28 24 7 11.983 VxxKxGEccCcC 41.9 6.3 138.2 14.47502 1.6458e−46 0.303184 0.045794 40 22 79.791 QxNT CeCC 22.2 3.4 31 10.89491 3.4768e−15 0.716129 0.108225 15 191 7 DxxGNG CccCCC 30 4.5 174.5 12.11783 3.3659e−16 0.17192 0.025984 2527 8 7 FPxxLT HHhhHH 19.4 3 59.9 9.792754 2.7723e−11 0.323873 0.04947822 8 1 3 FxTN EcCC 19.5 3 66.8 9.782338 3.5580e−11 0.291916 0.044669 1517 3 6 NxTPN HhCHH 18.4 2.8 46.3 9.571722 5.2061e−11 0.397408 0.06092818 13 1 5.818 AxKNG CcCCC 22.6 3.5 59.6 10.54578 4.7755e−13 0.3791950.058531 19 13 1 4.438 DSVT EEEE 20.6 3.2 45.4 10.11567 2.6490e−120.453744 0.070196 24 23 2 1.283 NTKVDK CEEEEE 28.8 4.5 135.4 11.725182.2882e−15 0.212703 0.032917 33 8 1 5.641 QxKEG HhHHC 24.5 3.8 61.110.93374 4.3327e−14 0.400982 0.06247 23 23 2 4.063 STKxDK CEEeEE 55.68.7 226.6 16.25592 1.6857e−58 0.245366 0.038248 61 14 1 4.5 STKVxKCEEEeE 58.5 9.1 226.5 16.68499 1.4066e−61 0.258278 0.040286 65 17 1 4.5NQxPN HHcHH 21.5 3.4 47.3 10.21015 1.1585e−12 0.454545 0.071654 20 16 15.828 GSTV CEEE 16.9 2.7 32.9 9.085333 1.8058e−10 0.513678 0.081151 1811 1 1.048 DxxxGS HhhhCC 20.9 3.3 65.1 9.930092 8.3751e−12 0.3210450.050797 19 22 13 8.933 YxxxxA HhhccH 22.8 3.6 74.5 10.28525 1.5427e−120.30604 0.048945 25 14 5 10.458 SxKVDK CeEEEE 55.6 9 226.6 15.848461.0626e−55 0.245366 0.039728 62 15 1 4.5 PPGxP CCCcC 24.9 4.1 88.410.60335 2.3088e−13 0.281674 0.045833 11 28 10 1.833 GIPxxQ CCChhH 17.92.9 69.3 8.960881 6.8872e−10 0.258297 0.042109 17 17 2 5.263 MDxS ECcC19.5 3.2 92.2 9.295372 2.0562e−10 0.211497 0.034591 20 13 5 6.204 NQTxNHHChH 17.4 2.9 46.3 8.87643 6.1701e−10 0.37581 0.061769 17 12 1 5.818WxGP CcHH 27.2 4.5 50.2 11.24573 5.9545e−16 0.541833 0.089269 25 30 104.972 DGDxQ CCCcC 26.3 4.4 66.8 10.81102 2.3355e−14 0.393713 0.065788 2917 3 1.25 STxVDK CEeEEE 58.1 9.7 253.5 15.8352 1.1831e−55 0.2291910.038304 65 14 1 5.5 QxxTN CecCC 17.9 3 30.2 9.063858 5.9222e−110.592715 0.099349 13 15 1 6 TKVDKK EEEEEE 65.1 11 336.5 16.61583.4212e−61 0.193462 0.032601 76 17 1 5.808 PFxA CCcH 20.8 3.5 66.69.47604 3.8082e−11 0.312312 0.052751 22 13 9 8.396 PPGP CCCC 25.6 4.382.9 10.4976 2.2505e−13 0.308806 0.052246 8 30 8 1 SSTKVD HCEEEE 37.46.3 196.6 12.53295 3.0773e−35 0.190234 0.032272 49 12 1 4.5 ISxxT CChhH29.2 5 113.2 11.13658 6.9787e−15 0.257951 0.043782 27 28 14 8.2 LxxNVCchHH 25.9 4.5 77.5 10.45325 1.5252e−13 0.334194 0.057583 22 19 4 1.542QSPxSL EECcEE 25 4.4 183.2 10.01805 2.8037e−12 0.136463 0.023753 32 15 23 LxAxxR CcHhhH 23.3 4.1 144.3 9.678385 1.6775e−11 0.161469 0.028167 2822 13 8.495 GxxxxN CechhH 25.6 4.5 93.3 10.15598 8.5365e−13 0.2743840.048505 29 24 4 4.774 QxxxxI EcceeE 27.5 4.9 130.6 10.40287 2.8316e−130.210567 0.037539 31 37 19 7 GFxN CChH 31.2 5.6 56.9 11.41646 2.1905e−290.54833 0.098116 29 24 3 5.26 NxxC EecC 27.3 4.9 112.3 10.362052.4035e−13 0.243099 0.043545 26 14 2 5.944 NxTxN HhChH 18.4 3.3 47.38.623012 6.9892e−10 0.389006 0.069712 18 13 1 5.818 RxxxxD EecceE 24 4.363.5 9.807516 1.3409e−12 0.377953 0.068037 23 29 16 6.716 NxxGV HhhCC22.3 4 70.5 9.365085 2.3344e−11 0.316312 0.057231 23 24 20 3.833 RxxMHhhE 19.4 3.5 58.8 8.698453 5.2415e−10 0.329932 0.060173 21 12 2 5.157AExxxV HHhhcC 21.2 3.9 171 8.898036 3.9391e−10 0.123977 0.022677 27 2925 6.033 NxKVDK CeEEEE 29.8 5.5 135.3 10.62519 1.1533e−25 0.2202510.040399 34 8 1 5.641 GLxxxQ CCchhH 54.6 10 239.5 14.37632 3.6957e−460.227975 0.041884 60 66 48 3.069 NTKxDK CEEeEE 28.8 5.3 135.4 10.419281.0158e−24 0.212703 0.039113 33 8 1 5.641 LxxxxM CchhhH 61.6 11.4 519.715.05731 1.4748e−50 0.11853 0.021888 66 64 35 9.681 FxxxxE EcchhH 34 6.3182.6 11.21745 1.6197e−28 0.186199 0.034562 36 42 30 14.833 SxKVxKCeEEeE 59.8 11.1 226.5 14.98264 4.7717e−50 0.264018 0.049037 67 18 1 4.5NTxVDK CEeEEE 28.8 5.4 135.9 10.34117 2.2370e−24 0.211921 0.039382 33 81 5.641 KQxT CEeE 26.1 4.9 50.9 10.13594 5.6397e−14 0.51277 0.095404 2525 2 2.517 QxxCS HhhHH 21.4 4 83.1 8.935147 1.8395e−10 0.257521 0.04799823 13 5 5.023 SxKxDK CeEeEE 56.6 10.6 226.5 14.5105 5.1077e−47 0.249890.046621 62 15 1 4.5 LxPxxR CcHhhH 39.9 7.4 228.2 12.08784 5.8061e−330.174847 0.032646 47 50 39 5.373 STxVxK CEeEeE 64 12 256.9 15.417596.1069e−53 0.249124 0.046526 71 19 1 5.5 GxPxxQ CcChhH 38.5 7.2 136.111.99353 1.9062e−32 0.28288 0.052856 41 40 19 6.991 NPxxxE CCchhH 30.15.6 135.5 10.53919 2.7481e−25 0.22214 0.041521 33 35 8 6.167 QTPN HCHH22.1 4.1 46.3 9.249495 8.5114e−12 0.477322 0.089425 22 16 1 7.818 ExGxSEcCcC 22.8 4.3 107 9.131379 8.1828e−11 0.213084 0.040032 25 20 3 6.266NTKVxK CEEEeE 29.8 5.6 135.4 10.43885 7.8103e−25 0.220089 0.041391 34 91 5.641 LSxxxH HHhhhH 34.7 6.5 227.6 11.16265 2.8341e−28 0.152460.028772 35 37 13 8.872 FPxxxT HHhhhH 22.4 4.2 81.3 9.076903 7.4347e−110.275523 0.052004 24 11 3 3 RxxxxY EecceE 25.3 4.8 101.4 9.5798665.9796e−12 0.249507 0.047384 25 27 18 8.5 KxxxxY EecceE 31.7 6 126.710.69146 5.1661e−26 0.250197 0.047719 32 33 28 10.2 GIxxxQ CCchhH 44.18.5 170 12.54746 1.8680e−35 0.259412 0.049891 38 36 14 7.463 QxRxxECcChhH 21.8 4.2 68.2 8.849948 1.4429e−10 0.319648 0.061734 24 25 8 2.818LCT CCC 29.6 5.8 90.5 10.25667 5.0074e−24 0.327072 0.063723 26 31 1711.287 PxVY CeEE 22.7 4.4 581 8.711344 7.2720e−10 0.039071 0.007627 3323 9 4.01 NPTE CCCH 21.3 4.2 69.4 8.654339 3.0076e−10 0.306916 0.06006922 18 2 1 STKxxK CEEeeE 60.5 11.8 226.5 14.52276 3.7939e−47 0.2671080.052292 66 18 1 4.5 MNxF CChH 25.2 4.9 62.4 9.506941 2.2013e−120.403846 0.079074 25 7 2 8.023 NVxxK EEccC 25.3 5 66 9.489538 2.9209e−120.383333 0.075233 25 12 3 5.523 KNVA EEEC 19.9 3.9 45.1 8.4472564.0013e−10 0.441242 0.086907 21 17 1 4.181 RxxxTD HcccCC 22.6 4.5 69.18.886497 9.5799e−11 0.327062 0.064487 29 27 6 7.032 EAxxAE HHhhHH 21.24.2 95.4 8.498906 7.3395e−10 0.222222 0.043919 21 22 20 4.5 VxxxNGEcccCC 29.1 5.8 121.9 9.97096 8.5736e−23 0.23872 0.047201 27 17 3 8.438RxxxD HhheC 21.4 4.2 67.2 8.614869 3.2608e−10 0.318452 0.063042 24 15 37.157 FNT ECC 25.2 5 90.3 9.30099 1.1273e−11 0.27907 0.055319 20 22 4 8TKxDKK EEeEEE 66.1 13.1 336.4 14.92853 8.7974e−50 0.196492 0.038972 7617 1 5.808 SSxKVD HCeEEE 38.4 7.7 196.6 11.32751 3.8624e−29 0.195320.038973 50 13 1 4.5 TKVxKK EEEeEE 65.1 13 336.5 14.73602 1.5202e−480.193462 0.038638 76 17 1 5.808 PxxLxV CceEeE 32.3 6.5 409.9 10.154811.1669e−23 0.0788 0.015954 36 29 6 6 YxxxNE HhhhHH 27.3 5.5 107.99.499449 8.3765e−21 0.253012 0.051287 28 30 14 7.268 LSxxxQ CChhhH 25.15.2 186.8 8.90443 1.9586e−18 0.134368 0.027613 26 30 21 2.125 KExxxACCchhH 25.3 5.2 85.5 9.049696 5.5135e−19 0.295906 0.061241 26 26 103.377 RxxDxD HhhCcC 36.6 7.6 188 10.735 2.5428e−26 0.194681 0.040444 3230 9 4.792 QxPxSL EeCcEE 27.9 5.8 253.4 9.267533 6.6594e−20 0.1101030.022941 36 18 2 3.5 SSTxVD HCEeEE 39.7 8.3 215.6 11.14276 2.7999e−280.184137 0.038369 52 13 1 5.5 TxVDKK EeEEEE 68.9 14.4 363.1 14.631516.3100e−48 0.189755 0.039746 80 17 1 6.808 QSPxxL EECceE 30.2 6.3 250.79.604652 2.6407e−21 0.120463 0.025266 39 21 3 3 CxNG CcCC 44.4 9.3 177.511.79647 1.4799e−31 0.250141 0.052558 43 35 13 12.179 DKEG HHHC 26.2 5.557.6 9.26898 7.4842e−20 0.454861 0.095656 26 26 3 4.063 STKVD CEEEE 61.613 230.1 13.90479 2.1619e−43 0.26771 0.056344 67 19 1 5 NxRG CeCC 26.15.5 50.1 9.307237 5.3638e−20 0.520958 0.109822 26 24 2 5.991 NIF CHH25.6 5.4 79.2 9.005026 8.0205e−19 0.323232 0.068183 25 10 3 11.435SSTKxD HCEEeE 37.9 8 196.6 10.78737 1.3832e−26 0.192777 0.040721 50 13 15.5 SxYQ ChHH 24.4 5.2 78.1 8.742181 8.3452e−18 0.31242 0.066298 21 32 50.238 QDxxG HHhhC 41.1 8.7 96 11.49502 5.3755e−30 0.428125 0.090888 3339 7 6.563 TKVDxK EEEEeE 65.5 14 338.5 14.09154 1.4697e−44 0.1935010.041227 76 17 1 5.808 LPxxxR CChhhH 31.2 6.7 201.9 9.644138 1.7359e−210.154532 0.033103 37 37 32 5 NxKxDK CeEeEE 29.8 6.4 135.4 9.4820968.5112e−21 0.220089 0.047229 34 8 1 5.641 CKxG CCcC 51.5 11.1 173.912.55874 1.2519e−35 0.296147 0.063651 47 32 7 11.923 VAxK ECcC 33.3 7.290.1 10.14773 1.2188e−23 0.369589 0.079833 30 14 1 6.435 EGxxY ECccC26.9 5.8 66.1 9.140516 2.2564e−19 0.406959 0.088175 25 23 3 9.785 AxxxGVHhhhCC 45.2 9.8 582.5 11.38712 1.5163e−29 0.077597 0.016857 52 51 4318.533 QSxxSL EEccEE 25 5.4 183.2 8.519344 5.1349e−17 0.136463 0.02966832 15 2 3 QxxxxT EecceE 35.6 7.8 134.6 10.29844 2.4065e−24 0.2644870.057628 35 41 27 8.758 LxPxxQ CcHhhH 26.4 5.8 169.7 8.748374 6.9214e−180.155569 0.033949 32 36 24 1 NVA EEC 38.6 8.4 107.2 10.80806 1.0942e−260.360075 0.07881 36 26 6 8.273 GFxxxD CCchhH 35.3 7.7 175.1 10.141681.1664e−23 0.201599 0.044152 40 44 23 9.865 SxxVDK CeeEEE 59.1 13.1253.5 13.08031 1.3690e−38 0.233136 0.051524 66 15 1 5.5 TNS HHH 28.8 6.4113.7 9.14901 1.8584e−19 0.253298 0.056008 26 18 3 4.21 QTxN HChH 22.14.9 48.3 8.202911 2.7740e−10 0.457557 0.10135 22 16 1 7.818 GxTN CcHH32.2 7.1 72.4 9.871338 1.9381e−22 0.444751 0.098713 31 24 4 6.255 NTxVxKCEeEeE 29.8 6.7 140.9 9.196737 1.1483e−19 0.211498 0.047197 34 9 1 5.641ACK CCC 43.1 9.6 105.9 11.30227 4.3157e−29 0.406988 0.091043 41 25 911.66 FxxxxY CchhhC 30.2 6.8 172.7 9.17886 1.3184e−19 0.17487 0.03924533 31 6 11 SxTKVD HcEEEE 55.5 12.5 313 12.41634 6.4044e−35 0.1773160.039921 70 18 1 8.833 IxxxxY EcceeE 25.5 5.7 229.8 8.350186 1.9949e−160.110966 0.024988 24 28 22 4.5 NxKVxK CeEEeE 30.8 6.9 138.8 9.2898264.7236e−20 0.221902 0.050018 35 9 1 5.641 NxxPN HhcHH 25 5.6 53.48.621938 2.2460e−17 0.468165 0.105585 23 19 1 6.331 WxxxxR CchhhH 33.47.5 151.7 9.659593 1.3620e−21 0.220171 0.049712 34 40 29 15.657 ExxxxREecceE 59.1 13.4 159.8 13.05759 1.8573e−38 0.369837 0.083731 54 72 4512.861 ACxN CCcC 23.9 5.4 105.8 8.125941 1.3307e−15 0.225898 0.051421 2218 3 6.049 GxSxxT CcChhH 25.9 5.9 139.5 8.40411 1.2643e−16 0.1856630.042356 29 23 20 4.411 QxPxxL EeCceE 34.6 7.9 344 9.568532 3.0272e−210.100581 0.023093 45 26 4 4.5 FxxxD HhhhC 60.3 13.9 504.8 12.627884.1362e−36 0.119453 0.027515 66 69 38 10.725 PxxY EhhH 37.8 8.7 161.410.12745 1.2193e−23 0.234201 0.054011 42 43 23 13.599 LxExxR CcHhhH 29.66.8 193.1 8.870479 2.0553e−18 0.153288 0.035373 38 40 33 4.292 SxKxxKCeEeeE 64 14.8 237.7 13.17977 3.3609e−39 0.269247 0.062429 69 21 2 4.5DSxT EEeE 32.3 7.5 89 9.470465 8.5068e−21 0.362921 0.084184 35 37 124.36 FPxxL HHhhH 39.1 9.1 187.5 10.21792 4.6988e−24 0.208533 0.048396 4628 8 9.363 AxxxGI HhhhCC 29.9 6.9 432.7 8.779901 4.3999e−18 0.0691010.016053 42 42 39 8.841 DxxGDG CccCCC 32.8 7.6 245.6 9.251579 6.0747e−200.13355 0.03109 31 37 12 4.958 NQxP HHcH 28.5 6.6 58 9.017809 6.1701e−190.491379 0.114435 26 23 3 7.849 QxPN HcHH 26.8 6.3 56.5 8.7053181.0034e−17 0.474336 0.110806 26 21 2 7.828 GxxL HhhE 23.9 5.6 86.17.996979 3.6702e−15 0.277584 0.065047 25 28 21 4.334 FxxxxR CchhhH 53.812.6 341.3 11.80788 9.6778e−32 0.157633 0.036994 62 65 53 14.205 ExxxxKHchhhH 29.4 6.9 82.3 8.942929 1.1236e−18 0.35723 0.083914 30 30 22 4GxxxxQ CcehhH 28.4 6.7 87.1 8.747114 6.3844e−18 0.326062 0.076678 29 3715 3.502 TKVDK EEEEE 86.3 20.3 363.4 15.07195 6.9306e−51 0.2374790.055879 98 24 1 10.141 LxxxxQ CchhhH 126.4 29.8 922.6 18.007174.5848e−72 0.137004 0.032258 140 158 106 19.556 NQxxN HHchH 21.5 5.147.3 7.729667 3.3269e−14 0.454545 0.107054 20 16 1 5.828 LxExxI CcHhhH31.2 7.4 297.3 8.889427 1.6173e−18 0.104945 0.024787 39 26 16 5.375VAxxN ECccC 25.5 6.1 95.8 8.160134 9.3058e−16 0.26618 0.063248 25 18 47.188 LxxxxR CchhhH 243 57.8 1351.9 24.88539 2.8521e−136 0.1797470.042782 264 293 196 44.49 PxNV ChHH 25.4 6.1 97.5 8.121634 1.2689e−150.260513 0.062064 23 28 9 3.542 TQSPxS EEECcE 21.5 5.1 177.4 7.3289576.0144e−13 0.121195 0.028944 26 14 2 2 QxxxSL EeccEE 27.9 6.7 256.28.321559 2.2276e−16 0.108899 0.026065 36 18 2 3.5 NxxVDK CeeEEE 29.8 7.1135.8 8.714799 7.8056e−18 0.21944 0.052559 34 8 1 5.641 AxxxxI HhhhcC71.2 17.1 836.7 13.23487 1.3942e−39 0.085096 0.020406 94 92 85 17.263NxxHQ HhhHH 21.3 5.1 62.2 7.471413 2.2332e−13 0.342444 0.082215 19 23 107.166 STxxDK CEeeEE 59.1 14.2 254.5 12.23358 5.4622e−34 0.23222 0.05596265 14 1 5.5 VxC EcC 60.4 14.6 326.9 12.28387 2.8734e−34 0.1847660.044568 54 41 12 14.71 STKxD CEEeE 64.9 15.7 230.1 12.88299 1.5164e−370.282051 0.0681 70 22 1 7 PxxxSA CceeEE 21.1 5.1 180.5 7.1811971.7416e−12 0.116898 0.028284 23 11 3 1.375 NTKVD CEEEE 32.3 7.8 136.39.001505 5.8508e−19 0.236977 0.057495 38 10 1 5.641 GVxF CEeE 20.8 5.1180.9 7.100474 3.1004e−12 0.114981 0.027956 21 22 16 8.469 DLxxxE CCchhH30.3 7.4 187.5 8.615766 1.7599e−17 0.1616 0.039316 34 38 29 9.749 SxKVDCeEEE 63.6 15.5 231.4 12.64685 3.0755e−36 0.274849 0.066994 68 21 1 5WxxxY CchhH 20.8 5.1 74 7.236102 1.2256e−12 0.281081 0.06854 19 33 148.479 NTKxxK CEEeeE 29.8 7.3 135.5 8.59084 2.2286e−17 0.219926 0.05364334 9 1 5.641 RxxxxR EecceE 20.5 5 75.5 7.172686 1.9425e−12 0.2715230.066234 20 25 19 3.583 RxRxG EcCcC 21.8 5.3 79.6 7.390263 3.8620e−130.273869 0.066905 22 25 19 4.833 YHxxxE HHhhhH 23.2 5.7 128.6 7.5160351.4229e−13 0.180404 0.044191 25 26 11 6.411 SSxKxD HCeEeE 38.9 9.5 196.69.744738 4.9097e−22 0.197864 0.048527 51 14 1 5.5 HxxNE HhhHH 36.8 9.1122 9.582928 2.4752e−21 0.301639 0.074219 36 40 15 9.644 LxDxxR CcHhhH24.5 6 159 7.656071 4.7140e−14 0.154088 0.038 27 31 23 4.616 NxTxxECcChhH 54 13.3 264.7 11.43435 7.0416e−30 0.204005 0.05034 54 67 29 8.762TxVxKK EeEeEE 68.9 17 371.5 12.85896 1.8898e−37 0.185464 0.04588 80 17 16.808 TKxDxK EEeEeE 66.5 16.5 338.4 12.64344 3.0096e−36 0.196513 0.0486576 17 1 5.808 RxxDxS EccCcC 20.5 5.1 138.7 6.97113 7.6462e−12 0.1478010.036621 27 29 20 3.827 QDKE HHHH 23.7 5.9 64 7.716774 3.1832e−140.370312 0.091796 22 22 1 4.063 GxxF EccE 28.3 7 152 8.219089 5.0381e−160.186184 0.046217 30 34 19 9.566 QSPxS EECcE 30.2 7.5 200.3 8.4502797.0338e−17 0.150774 0.037434 37 20 3 3 NLxxxD CCchhH 24.9 6.2 242.57.619062 6.0600e−14 0.10268 0.025522 26 29 21 11 YxxxxP EecceE 23.8 5.9118.9 7.53558 1.1961e−13 0.200168 0.049815 27 35 21 2.963 LxExxK CcHhhH24.2 6 184.2 7.523785 1.2703e−13 0.131379 0.032735 30 32 30 6.2 MxIxECcHhH 20.5 5.1 117.7 6.943104 9.2565e−12 0.174172 0.043553 25 14 9 8.328GxExF CcCeE 20.1 5 116.8 6.848623 1.7824e−11 0.172089 0.043222 24 21 44.684 GxTxxQ CcChhH 51.1 12.8 261.6 10.9496 1.6032e−27 0.195336 0.04908263 74 55 7.462 ExxPxD HhcCcC 20.1 5.1 88.6 6.882766 1.4270e−11 0.2268620.05714 20 24 16 2.25 MNxxD CChhH 22.2 5.6 69.2 7.324761 6.0496e−130.320809 0.080818 17 23 13 3.584 FNxN ECcC 20.7 5.2 107.5 6.9506368.7080e−12 0.192558 0.04852 16 18 5 6 NxCN CcCC 27.4 6.9 110.2 8.0559121.9302e−15 0.248639 0.062659 28 34 10 5.048 MxxxxP EecceE 21.2 5.3 84.57.081721 3.4833e−12 0.250888 0.063298 26 22 9 2.75 FxxxxD EcchhH 20.75.2 160.7 6.880946 1.3823e−11 0.128811 0.032525 23 24 16 7.715 RxxxPEHhhcCC 28.5 7.2 111.5 8.193404 6.1741e−16 0.255605 0.064712 30 27 223.901 GSxxE CEeeE 20.3 5.1 75.4 6.918189 1.1167e−11 0.269231 0.068279 2216 6 2.048 NxAL ChHH 30.5 7.7 168.3 8.377216 1.2719e−16 0.181224 0.0459830 33 27 6.667 SxxVxK CeeEeE 65.3 16.6 303.8 12.30932 1.9144e−340.214944 0.054555 73 20 1 5.5 RxxGxA HhhCcC 21.2 5.4 114.5 6.9857456.6680e−12 0.185153 0.046994 27 33 21 2.833 LTxxxK CChhhH 29.4 7.5 198.18.18312 6.3961e−16 0.14841 0.037688 33 33 28 5.063 IxxxxR CchhhH 79.220.1 469.1 13.46389 5.9268e−41 0.168834 0.042888 88 90 67 14.891 KNxAEEeC 20.4 5.2 50.6 7.054783 4.4588e−12 0.403162 0.102437 21 17 1 4.181SLxxxE CCchhH 36.6 9.3 220.9 9.134791 1.5180e−19 0.165686 0.042167 41 4629 5.65 AxxSQ HhhHC 32.8 8.4 98.7 8.827817 2.6401e−18 0.33232 0.08479 3327 10 3.798 KxxxLD HhccCC 25.2 6.4 158 7.548711 1.0095e−13 0.1594940.040754 29 27 16 3.182 VQxxxS ECcccC 25.7 6.6 164.8 7.619327 5.8468e−140.155947 0.03985 27 26 2 0.5 FTN CHH 29.5 7.6 58.8 8.553956 3.1605e−170.501701 0.128453 27 20 1 5.263 QxxEG HhhHC 34.9 8.9 104.9 9.070132.9112e−19 0.332698 0.085314 32 38 8 8.463 GFT CCH 31.4 8.1 73.38.717496 7.2684e−18 0.428377 0.109906 30 23 3 5.255 GxDxxQ CcChhH 29 7.4147.4 8.106973 1.1979e−15 0.196744 0.05051 30 28 20 7.667 LTxxxR CChhhH30.4 7.8 203.9 8.238198 3.9476e−16 0.149093 0.038329 33 36 29 3.333 DxEGHhHC 38.2 9.8 91.3 9.586215 2.3137e−21 0.418401 0.107564 37 43 13 7.397NAxxxQ HHhhhH 20.6 5.3 129.5 6.788754 2.5681e−11 0.159073 0.040908 19 2316 8 QSxxxL EEcceE 30.2 7.8 260.2 8.169296 6.9027e−16 0.116065 0.02986339 21 3 3 GxSxxA CcChhH 30.1 7.8 260.9 8.142754 8.5659e−16 0.115370.029738 32 35 28 9.081 TVxxxE CHhhhH 24.2 6.2 110.1 7.40446 3.0474e−130.2198 0.056658 26 20 19 5 SKxxH HHhhH 34 8.8 105.4 8.902407 1.3189e−180.322581 0.083153 32 43 14 6.807 CxP ChH 38.6 10 195.9 9.3189722.6851e−20 0.197039 0.050815 41 47 21 8.789 YxxEN HhhHH 47.1 12.1 158.410.43551 4.0653e−25 0.297348 0.076699 47 58 23 3.68 YxxxxE EechhH 27.57.1 135.1 7.864945 8.4555e−15 0.203553 0.052558 32 28 16 4.787 SxSxxACcChhH 28.4 7.3 190 7.931919 4.8305e−15 0.149474 0.038609 34 33 18 4.015SxxGL HhhCC 27.2 7 120.2 7.839361 1.0445e−14 0.22629 0.058491 31 36 273.572 DxAxxQ ChHhhH 30.4 7.9 151.2 8.256938 3.4079e−16 0.201058 0.05198632 39 30 5.433 ExxxxY EcceeE 29.7 7.7 170.1 8.125602 1.0025e−15 0.1746030.045189 32 34 27 6.45 ExDxxG HhCccC 20.8 5.4 144.5 6.752501 3.2182e−110.143945 0.037384 18 19 7 4 RxKxG EcCcC 27.1 7.1 109.2 7.7817321.6320e−14 0.248168 0.064822 25 28 18 11.209 TxVDxK EeEEeE 69.3 18.1368.2 12.32308 1.5043e−34 0.188213 0.049248 80 17 1 6.808 GxxxxF EecceE33.3 8.7 334 8.43651 6.9899e−17 0.099701 0.026101 45 60 8 3.924 CKN CCC43.3 11.3 142.4 9.894711 1.0185e−22 0.304073 0.079616 39 34 8 12.606YxxxE EchhH 25.1 6.6 100 7.466048 1.8730e−13 0.251 0.06584 25 29 207.899 AxxxxV HhhhcC 87.4 23 1099.8 13.58946 9.7121e−42 0.079469 0.020879114 119 101 28.431 LSxxY HHhhH 44.5 11.7 344 9.754079 3.7941e−22 0.129360.034022 37 45 14 7.408 TKVxK EEEeE 92.3 24.5 367.4 14.17006 3.0926e−450.251225 0.066733 105 29 1 10.141 DxxRN HhhHC 24.5 6.5 74.9 7.380533.6042e−13 0.327103 0.086891 26 24 19 6.5 SSTKV HCEEE 41.4 11 198.19.427547 9.0951e−21 0.208985 0.055556 52 15 1 4.536 GVxxxE CCchhH 38.310.2 238.7 8.992735 5.1079e−19 0.160452 0.042731 43 51 37 5.901 ExxNSHhhHC 18.8 5 57.3 6.447436 2.5887e−10 0.328098 0.087466 18 21 16 3 DxDxTCcCcE 20.6 5.5 97.6 6.635209 7.0133e−11 0.211066 0.05628 18 21 8 6.515NLY CHH 19.2 5.1 58 6.509825 1.7088e−10 0.331034 0.088392 18 20 17 3YxGD EeCC 25.4 6.8 119.1 7.343589 4.4620e−13 0.213266 0.057113 29 28 217.501 SxxWPS CccCCC 19.8 5.3 162.2 6.396654 3.2879e−10 0.122072 0.03271923 22 1 4 ELxxxE CCchhH 27.3 7.3 172.9 7.544366 9.5073e−14 0.1578950.042349 28 29 21 2 SxTxVD HcEeEE 57.7 15.5 332.4 10.97081 1.1028e−270.173586 0.046666 73 19 1 9.833 TxxDKK EeeEEE 69.9 18.8 364 12.105622.0737e−33 0.192033 0.05163 80 17 1 6.808 SAGT CCCC 18.8 5.1 65.46.36097 4.4071e−10 0.287462 0.077343 20 24 9 6.286 NPxE CCcH 23.8 6.492.8 7.124827 2.2574e−12 0.256466 0.069004 25 21 5 1 TQxPxS EEeCcE 25.86.9 245.4 7.260776 7.8442e−13 0.105134 0.028289 32 17 2 2.5 DxSV EeEE19.1 5.1 128.3 6.281303 6.9655e−10 0.14887 0.040088 22 19 16 2.25 GVxxxDCCchhH 23.4 6.3 189.3 6.92795 8.7577e−12 0.123613 0.033287 24 27 226.057 QxxxxT CccecC 24.6 6.6 81.9 7.279091 7.3895e−13 0.300366 0.08096328 27 10 2.904 RxxxxT EecceE 23.5 6.4 116.1 6.994801 5.5755e−12 0.2024120.054742 20 27 19 8.114 YxxxNR EcccEE 19.8 5.4 85.3 6.438949 2.5510e−100.232122 0.062882 21 18 2 4.356 NKxG HHhC 32.2 8.7 87.3 8.3776821.2095e−16 0.368843 0.099933 33 36 27 4.271 CxH ChH 22.2 6 117.76.772808 2.6270e−11 0.188615 0.051121 24 22 17 5 NVM HHH 22.3 6 170.96.72985 3.4499e−11 0.130486 0.035381 22 16 4 3.542 ExxI HhhE 29.5 8120.6 7.861338 8.0506e−15 0.24461 0.06639 31 36 25 5.111 STxVD CEeEE66.1 17.9 259 11.78422 9.9807e−32 0.255212 0.069278 72 20 1 6 KVDKKEEEEE 71.2 19.4 341.6 12.13106 1.4989e−33 0.208431 0.056672 81 22 15.808 SGxW CCcE 20.7 5.6 91.2 6.551699 1.1925e−10 0.226974 0.06179 21 2318 7.5 NTxxDK CEeeEE 28.8 7.8 135.9 7.708178 2.6509e−14 0.2119210.057719 33 8 1 5.641 DxVT EeEE 24.9 6.8 171 7.088115 2.7435e−120.145614 0.039734 31 34 9 1.708 YNN ECC 19.7 5.4 60.5 6.4723672.0995e−10 0.32562 0.088854 17 26 9 6.123 PxTxxQ CcChhH 21.7 5.9 173.76.591601 8.7031e−11 0.124928 0.034126 30 33 20 5.625 GxxGF HhhCC 22.1 6100.2 6.742831 3.2248e−11 0.220559 0.060261 29 16 6 4.26 LDxxxR CChhhH32.5 8.9 240.5 8.068869 1.4172e−15 0.135135 0.036966 38 32 13 6.644NxKVD CeEEE 34.1 9.4 138.3 8.361157 1.2840e−16 0.246565 0.067811 41 12 15.641 STxxxK CEeeeE 68 18.7 273.9 11.80545 7.5425e−32 0.248266 0.0683174 22 3 5.5 ExxHD HhhHH 21.8 6 82.4 6.70029 4.3412e−11 0.264563 0.07279721 22 13 5.667 DxNxY CcCcE 20.3 5.6 84.7 6.441134 2.4504e−10 0.2396690.065956 24 17 7 1.375 DxxGxP HhhCcC 33.8 9.3 183 8.241246 3.4292e−160.184699 0.050855 38 39 19 4.333 SxxxxN CceccE 20.4 5.6 67.2 6.5153351.5374e−10 0.303571 0.083593 25 26 5 5.606 FxxM ChhH 32.3 8.9 164.38.052618 1.6312e−15 0.196592 0.054268 37 32 17 8.547 SPSSL ECCEE 22.66.2 113.2 6.737919 3.2449e−11 0.199647 0.05512 25 10 1 0 WxxxxT HhhccC21.1 5.8 171.2 6.436797 2.3915e−10 0.123248 0.034041 27 24 20 3.9 ESYEEE 19.3 5.3 85.3 6.240198 8.9001e−10 0.22626 0.062595 17 20 10 8.5SxTKxD HcEEeE 56 15.5 313 10.55562 9.5006e−26 0.178914 0.049499 71 19 19.833 VxxKN EccCC 29.4 8.2 105.5 7.747512 1.9363e−14 0.278673 0.07726728 18 3 8.188 GxxxDF EeccEE 25.3 7 248.3 6.995039 5.0997e−12 0.1018930.028291 34 35 3 0 RxxxTG EeccCC 24.8 6.9 127.8 7.018198 4.4794e−120.194053 0.053883 30 33 18 1.284 VxxGA HhcCC 33.4 9.3 235.9 8.0765371.2963e−15 0.141585 0.039348 39 40 37 4.283 QxPxS EeCcE 34.5 9.6 273.28.163922 6.2295e−16 0.126281 0.035226 43 23 3 3.5 LxxxxK CchhhH 149.341.7 947.4 17.0475 7.0481e−65 0.157589 0.043999 173 204 157 23.953SxAxxR ChHhhH 47.9 13.4 257.1 9.69243 6.3584e−22 0.186309 0.052044 49 5024 4.47 ExxxxL EecceE 40.3 11.3 277.3 8.826998 2.0686e−18 0.145330.040651 35 41 22 9.5 YxxxxY EcceeE 26 7.3 256.4 7.038223 3.6866e−120.101404 0.028396 31 34 24 10.368 NxSxxD CcChhH 25.1 7 145.6 6.9799425.7351e−12 0.17239 0.048331 28 28 22 4.334 PGxxA CChhH 28.5 8 157.57.44514 1.8844e−13 0.180952 0.050747 32 27 20 2.951 LSxxxI CChhhH 25.47.1 404.3 6.907684 9.1681e−12 0.062825 0.017623 27 30 22 3.343 PNR HHH26.3 7.4 104.2 7.227147 9.8791e−13 0.252399 0.070802 28 23 6 10.321FxxEE HhhHH 21.3 6 123.9 6.403548 2.9275e−10 0.171913 0.048423 23 25 195.976 RxHG HhHC 25.6 7.2 82.9 7.166051 1.5713e−12 0.308806 0.086994 3233 30 6.25 QxxxxL EecceE 42.9 12.1 459.9 8.96776 5.6147e−19 0.0932810.026328 53 36 12 5.5 RxxxGL HhhhCC 28.6 8.1 176.7 7.393568 2.7275e−130.161856 0.045701 32 34 21 5.7 GLxxxE CCchhH 55.6 15.7 370.9 10.286611.5314e−24 0.149906 0.042345 55 64 53 14.726 DxxRG CceCC 21.2 6 58.36.559553 1.1201e−10 0.363636 0.102768 24 19 1 4.782 YxxxxK EecceE 23.26.6 106.7 6.708479 3.8350e−11 0.217432 0.061457 25 30 21 4.75 FxxS ChhH46.5 13.2 250.8 9.432711 7.6287e−21 0.185407 0.052529 51 43 21 7.676TQxG HHcC 23.6 6.7 73 6.85765 1.4179e−11 0.323288 0.091676 26 32 213.847 SxKxD CeEeE 66.9 19 237.4 11.47017 3.6870e−30 0.281803 0.079926 7124 1 7 SxxWxS CccCcC 23.6 6.7 200.2 6.644325 5.6746e−11 0.1178820.033448 26 26 4 6 VPS CHH 23.5 6.7 71.3 6.843087 1.5709e−11 0.3295930.093573 20 23 13 6 FxxxLT HhhhHH 24 6.8 425 6.631623 6.0285e−110.056471 0.016048 27 14 6 5.5 SSTxxD HCEeeE 40.2 11.4 216.6 8.7397294.4322e−18 0.185596 0.052797 53 14 1 6.5 YDY CCE 24.7 7 113 6.8713791.2210e−11 0.218584 0.062322 22 28 12 4.25 LSxxxR CChhhH 40.4 11.5 293.28.662063 8.5519e−18 0.13779 0.039389 48 58 43 12.646 EQF CEE 23.4 6.779.4 6.738533 3.1440e−11 0.29471 0.084441 26 26 4 4.684 TxVDK EeEEE 9025.8 396 13.07771 8.3835e−39 0.227273 0.065121 102 24 1 11.141 ETxS ECcC29.2 8.4 99.1 7.526295 1.0238e−13 0.294652 0.084439 27 26 9 13.54 LxxGYHhcCC 25.2 7.2 158.7 6.845655 1.4142e−11 0.15879 0.045521 24 29 23 9.094TKVxxK EEEeeE 66 18.9 393 11.08834 2.6474e−28 0.167939 0.048171 77 18 25.808 IAxxG HHhhC 23.8 6.8 183.8 6.617026 6.7222e−11 0.129489 0.03716325 31 22 2.501 LxxxGV HhhhCC 23 6.6 445.9 6.430108 2.2726e−10 0.0515810.014805 27 29 25 6.833 YxxM CccE 28.9 8.3 165.3 7.338177 4.0315e−130.174834 0.050202 31 30 8 7.862 MxxxxY CchhhH 22.2 6.4 219.9 6.3558833.7539e−10 0.100955 0.029014 23 26 20 2 NxxxxT EccccE 26.5 7.6 179.96.984374 5.2547e−12 0.147304 0.04239 30 37 20 12.06 TxAxxK ChHhhH 33.79.7 179.1 7.910811 4.7461e−15 0.188163 0.054259 35 37 26 11.06 WxxxxKHhhhcC 38.8 11.2 266.7 8.429782 6.3105e−17 0.145482 0.041973 47 49 296.095 PxSS EhHH 21.2 6.1 94.8 6.304806 5.4447e−10 0.223629 0.064531 2425 4 3.333 TKxDK EEeEE 87.3 25.2 364.3 12.81001 2.7096e−37 0.2396380.069249 98 24 1 10.141 QxKxG HhHhC 36 10.4 188.4 8.142734 7.1133e−160.191083 0.055388 34 36 11 5.063 SxxKVD HceEEE 56.5 16.4 313 10.172344.8080e−24 0.180511 0.052395 71 19 1 8.833 IDxS ECcE 41.4 12 221.98.712627 5.4346e−18 0.186571 0.054175 49 41 2 4.361 PTxxxL CChhhH 23 6.7322.9 6.377182 3.1697e−10 0.071229 0.0207 23 22 12 4.833 FxxH CccH 216.1 86.6 6.254237 7.5023e−10 0.242494 0.070478 21 16 10 0.021 LxxxxPEecceE 22.6 6.6 152.9 6.393634 2.9287e−10 0.147809 0.042963 25 27 20 4.5RxxxxE EecceE 36.6 10.6 131.4 8.30223 1.9387e−16 0.278539 0.080969 44 5239 10.524 QTxxxK HHhhhH 25.6 7.4 144 6.832254 1.5255e−11 0.1777780.051705 24 28 17 4.636 LxxxxV HccccE 24.2 7 365.7 6.531652 1.1388e−100.066174 0.019247 26 26 21 4.9 DxNxE CcChH 25.1 7.3 128.5 6.7816852.1820e−11 0.195331 0.056827 25 31 20 4.226 TxTxxE CcChhH 30.8 9 191.47.468604 1.4651e−13 0.16092 0.046846 35 33 29 6.084 TKxxKK EEeeEE 66.119.3 341.6 10.99212 7.5992e−28 0.193501 0.056354 76 17 1 5.808 MNxxECChhH 44.6 13 167.5 9.123343 1.3666e−19 0.266269 0.077633 46 33 16 9.479ExxxxR EcceeE 39.2 11.5 139.1 8.542044 2.4730e−17 0.281812 0.082523 3947 29 4.741 ANxxN HHhhH 26.8 7.9 128.3 6.978653 5.4345e−12 0.2088850.061203 29 34 25 6.133 NxxxxW CccccE 25.7 7.5 182.6 6.748517 2.6433e−110.140745 0.041333 26 33 18 9.452 ExxGxS HhcCcC 24.9 7.3 129.6 6.682724.2194e−11 0.19213 0.056545 27 30 23 9.63 QxxxxM CcchhH 24.2 7.1 1546.5474 1.0378e−10 0.157143 0.046288 27 21 12 1.75 ExxGxS HhhCcC 35.410.4 185.6 7.959755 3.0861e−15 0.190733 0.056187 37 39 35 7.367 VxxxxFCchhhH 40.9 12.1 688.2 8.38324 8.7602e−17 0.05943 0.017513 51 68 3916.33 LSxxxK CChhhH 29.4 8.7 241 7.163028 1.3727e−12 0.121992 0.03601633 42 31 5.338 MNI CCH 22.6 6.7 70.6 6.475222 1.7836e−10 0.3201130.094588 23 9 4 8.685 GxSxxE CcChhH 92.3 27.3 563.9 12.76202 4.6873e−370.163682 0.048374 106 122 100 25.005 SxxxDK CeeeEE 60.1 17.8 256.610.37493 5.7844e−25 0.234217 0.069505 66 15 1 5.5 NxAxxK ChHhhH 23.7 7.1137.1 6.437742 2.1271e−10 0.172867 0.051429 26 30 19 6.25 SPxSL ECcEE42.9 12.8 185.7 8.74043 4.1484e−18 0.231018 0.068739 49 26 2 4 QxTG HhHC36.3 10.8 146.5 8.059476 1.3787e−15 0.247782 0.073749 40 36 23 9.267NxKxxK CeEeeE 32.2 9.6 154 7.535957 8.5785e−14 0.209091 0.062307 37 12 35.641 NTKxD CEEeE 32.3 9.6 139.1 7.572258 6.5452e−14 0.232207 0.06922938 10 1 5.641 YxxxF HhhcC 33.4 10 178.8 7.634612 3.9592e−14 0.1868010.055774 31 41 27 14.079 GRxxxE CCchhH 25.7 7.7 147.8 6.68039 4.1501e−110.173884 0.051943 31 30 28 5.267 LPxxV CChhH 31.7 9.5 328.1 7.313764.3680e−13 0.096617 0.028935 31 31 18 5.61 ExxxxV EcceeE 46.8 14 318.48.939876 6.6359e−19 0.146985 0.044109 54 55 39 6.26 AxxxGA HhhhCC 26.98.1 515.8 6.675596 4.0624e−11 0.052152 0.015659 32 38 29 11.774 RxxLHhhE 32.4 9.7 158.9 7.491324 1.1856e−13 0.203902 0.061321 35 36 19 3.333AxxGxP HhcCcC 32.9 9.9 247.6 7.451189 1.5600e−13 0.132876 0.040039 40 4434 7.278 FxxxxK CchhhH 35.7 10.8 264.1 7.751308 1.5295e−14 0.1351760.040809 41 45 36 8.614 QTP HCH 22.1 6.7 47.9 6.42922 2.4745e−100.461378 0.139514 22 16 1 7.831 KxxGF HhcCC 37.3 11.3 204.8 7.9694612.7196e−15 0.182129 0.055082 44 44 34 8.977 NTxVD CEeEE 32.3 9.8 136.87.475662 1.3386e−13 0.236111 0.071465 38 10 1 5.641 SSxxVD HCeeEE 40.712.3 215.6 8.311402 1.6093e−16 0.188776 0.057261 53 14 1 5.5 GxSxxQCcChhH 32.5 9.9 203.2 7.392465 2.4290e−13 0.159941 0.048517 38 46 323.241 MxxxxL HhhccC 37.8 11.5 525 7.853004 6.6035e−15 0.072 0.021871 4652 41 8.19 NxLP HhCC 31.4 9.5 153.2 7.304107 4.7698e−13 0.2049610.062314 35 40 29 7.155 DxxSN HhhHH 31 9.4 133.5 7.288476 5.4139e−130.23221 0.070612 29 34 21 3.4 DRC CCC 32.2 9.8 128.7 7.444459 1.6904e−130.250194 0.076146 35 28 13 11.164 ExxxxK EcceeE 43.1 13.1 168.8 8.6063011.3067e−17 0.255332 0.077849 46 60 39 3.758 RxxFV HhhHH 24.5 7.5 193.46.343231 3.7108e−10 0.12668 0.038702 26 20 5 3.886 HxxxxR CchhhH 42.212.9 198.2 8.441254 5.3279e−17 0.212916 0.065049 44 48 33 16.485 SxxDSHhhHH 28.9 8.9 121.4 6.997453 4.4603e−12 0.238056 0.072925 31 35 296.813 SxW ChH 89.6 27.5 434.3 12.254 2.6846e−34 0.206309 0.063216 84 9142 39.624 TxSxxE CcChhH 26.4 8.1 188.8 6.57813 7.8469e−11 0.1398310.042863 31 34 29 3.467 ExxLP HhhCC 31.6 9.7 176.5 7.229156 8.0852e−130.179037 0.054991 30 32 26 7.579 ExxxxT EecceE 36.9 11.3 146.3 7.8991994.7926e−15 0.252221 0.07755 41 43 32 7.786 TQA CHH 28.7 8.8 79.57.084686 2.4870e−12 0.361006 0.111203 29 33 24 7.459 YxxxxQ EccccC 41.712.9 277.2 8.238435 2.8485e−16 0.150433 0.046375 43 47 27 9.222 RIxxNHHhhH 31.3 9.7 211.7 7.132289 1.6125e−12 0.147851 0.045594 32 23 1510.306 DxSQ EcCC 24.6 7.6 83.1 6.463222 1.7704e−10 0.296029 0.091555 2325 12 3.077 RxxGI HhcCC 41 12.7 265.2 8.142027 6.3123e−16 0.15460.047865 52 60 49 6.078 KxxGxN HhcCcC 33.4 10.3 186.4 7.3751822.6922e−13 0.179185 0.055503 38 41 22 3.053 ExxAA HhhHC 52.1 16.1 2149.306055 2.2237e−20 0.243458 0.075445 64 66 52 8.575 SxxxxY HhhccC 32.310 223.4 7.202382 9.5601e−13 0.144584 0.044849 33 37 30 10.279 WxxP CchH45.8 14.2 136.8 8.84778 1.5505e−18 0.334795 0.103937 44 60 23 12.363ExxxAL HhhhHC 32.2 10 257.3 7.160501 1.2869e−12 0.125146 0.038867 37 3630 1.667 RxxxD CechH 23.6 7.4 54.6 6.44067 2.1538e−10 0.432234 0.13467722 29 8 2.167 AxxxGL HhhhCC 28.1 8.8 473.3 6.596022 6.5719e−11 0.059370.018507 34 33 33 6.75 WxG CcH 47.8 14.9 153.6 8.967722 5.1676e−190.311198 0.097025 43 51 23 13.556 ExSxxE CcChhH 46.7 14.6 297.5 8.6317269.6940e−18 0.156975 0.048973 50 50 40 11.231 RxxI HhhE 27 8.4 142.76.580268 7.6218e−11 0.189208 0.059204 28 28 18 4.75 KxF CeC 35.5 11.1146.1 7.608196 4.5904e−14 0.242984 0.076091 40 51 16 6.317 TxAxxR ChHhhH26 8.1 178.9 6.402991 2.4282e−10 0.145333 0.045534 26 30 25 5.688 AxGxRHcCcC 36.6 11.5 170.4 7.680274 2.5874e−14 0.214789 0.06734 42 47 3910.232 RxxGxN HhcCcC 27.5 8.6 166 6.600575 6.5622e−11 0.165663 0.05195932 37 18 2 LxxxxI CchhhH 120.9 37.9 1893.1 13.6104 5.3167e−42 0.0638640.020034 139 130 97 17.117 EDxxY HHhhH 34.2 10.8 168.1 7.3910772.3540e−13 0.20345 0.063963 35 37 20 1.694 NxxSL HhhHH 28.2 8.9 193.66.646094 4.7656e−11 0.145661 0.045803 30 31 23 5.507 LNxxQ CChhH 24.67.7 175.6 6.199337 8.9664e−10 0.140091 0.04407 27 29 23 9.015 KxDKKEeEEE 72.2 22.8 341.6 10.7017 1.5998e−26 0.211358 0.066796 81 22 1 5.808KxxGA HhcCC 44 13.9 283.3 8.262977 2.2260e−16 0.155312 0.049167 55 68 455.091 TxAxxE ChHhhH 42.1 13.3 254.5 8.093575 9.1094e−16 0.1654220.052386 46 44 34 5.667 VxxxxQ CchhhH 41.1 13 292.8 7.955165 2.7819e−150.140369 0.044502 47 59 39 8.622 DSV EEE 27 8.6 127.2 6.5217391.1133e−10 0.212264 0.067344 32 31 8 3.083 GxxxxQ CcchhH 255.1 81.21223.1 19.98054 1.2830e−88 0.208568 0.066361 268 302 205 46.327 SxxxxVHhhhcC 35.4 11.3 332.5 7.310744 4.0564e−13 0.106466 0.033905 46 47 407.398 NxxRN HhhHH 33.2 10.6 140.1 7.23656 7.3844e−13 0.236974 0.07547437 38 27 5.133 YxxxN HhhhH 359.7 114.6 1469.5 23.8353 2.2944e−1250.244777 0.078017 311 417 220 77.817 SAxxxR CHhhhH 38.1 12.2 224.67.644138 3.2710e−14 0.169635 0.054175 38 37 21 5.834 EGxT ECcE 26.5 8.578 6.552315 9.4222e−11 0.339744 0.10876 28 30 15 1.51 LxxxxY CchhhH 4213.5 555.3 7.880036 4.8923e−15 0.075635 0.024224 52 50 41 8.542 TxxxxWCchhhH 26.8 8.6 193.7 6.357807 3.1394e−10 0.138358 0.044331 32 27 139.251 ExxxxP EecceE 34.5 11.1 144.7 7.333049 3.5729e−13 0.2384240.076446 38 41 32 2.484 AxxxxR CchhhH 115.3 37 706.6 13.22827 9.2344e−400.163176 0.052343 125 142 105 26.714 LGF HCC 32.9 10.6 200.8 7.0635062.5027e−12 0.163845 0.052585 37 40 32 5.018 ITxxQ CChhH 28.7 9.2 1896.582122 7.1234e−11 0.151852 0.04875 34 34 28 11.232 TxxxxR CchhhH 97.231.2 509.4 12.1895 5.4680e−34 0.190813 0.061279 107 125 93 23.513 STKVCEEE 69.5 22.3 234.9 10.49468 1.4747e−25 0.295871 0.095048 75 24 1 5.036IxxxxY CchhhH 27.2 8.7 372.9 6.318022 3.9509e−10 0.072942 0.02344 36 3636 7.75 SPxxLS ECceEE 30 9.7 170.2 6.744862 2.3659e−11 0.176263 0.05669835 22 2 1 ALS EEE 27 8.7 349.5 6.287868 4.7936e−10 0.077253 0.024873 3029 17 1.825 FxxxE EehhH 30.6 9.9 170.7 6.807095 1.5366e−11 0.1792620.057738 35 38 21 7.082 SxxxxQ CchhhH 107.1 34.6 557.3 12.734685.8204e−37 0.192177 0.062044 123 129 80 29.468 SxxPG HhcCC 30 9.7 107.96.839335 1.2706e−11 0.278035 0.089798 34 38 14 6.743 TVA CHH 40.3 13 1377.949197 3.0102e−15 0.294161 0.095013 42 40 29 10.153 KxHG HhHC 25.4 8.285.6 6.310346 4.4829e−10 0.296729 0.095898 29 33 23 6.286 DxPxY CcCcC26.5 8.6 158 6.299163 4.5765e−10 0.167722 0.05423 26 30 15 2.875 SSTxVHCEeE 44.7 14.5 217.1 8.214938 3.2657e−16 0.205896 0.066745 56 16 15.536 SSxKV HCeEE 42.6 13.8 198 8.026654 1.5452e−15 0.215152 0.0698 5417 1 4.536 NTxxxK CEeeeE 33.8 11 168.6 7.116682 1.6931e−12 0.2004740.065182 38 13 4 6.141 LPxxQ CChhH 26 8.5 150.9 6.209625 8.0645e−100.1723 0.056038 27 29 24 6.067 SxTxxE CcChhH 26.3 8.6 179.1 6.2101327.9457e−10 0.146845 0.047823 35 32 21 6.641 PxSQ ChHH 31.3 10.2 1116.920163 7.0916e−12 0.281982 0.092073 33 39 25 6.917 YxxxxR EccceE 4213.7 199.7 7.912163 3.8543e−15 0.210315 0.068697 48 46 8 9.456 PxxLTHhhHH 34.7 11.3 229.3 7.111345 1.7124e−12 0.15133 0.049482 34 19 6 4.5WxxxxK CchhhH 33.1 10.8 143.7 7.034008 3.0769e−12 0.230341 0.075405 3943 23 7.556 SxTKV HcEEE 63.7 20.9 316.4 9.703558 4.3917e−22 0.2013270.065941 79 26 1 9.869 WxxxE CchhH 64.8 21.2 274 9.845227 1.0984e−220.236496 0.077482 62 77 54 16.611 YxxxH HhhhC 112.7 36.9 440.2 13.021591.4162e−38 0.25602 0.083929 129 149 109 34.612 SAxxxK CHhhhH 30 9.9163.6 6.620898 5.3547e−11 0.183374 0.060226 32 39 22 6 PVxxA HHhhH 42.914.1 430.6 7.802016 8.8311e−15 0.099628 0.03273 42 46 28 3.2 LxxxxIHhhccC 81.5 26.8 1641 10.66137 2.1892e−26 0.049665 0.016319 99 104 9018.507 NxxxDK CeeeEE 29.8 9.8 140.6 6.628627 5.1332e−11 0.2119490.069648 34 8 1 5.641 SxLP HhCC 41.8 13.8 235.1 7.791006 9.8874e−150.177797 0.058524 47 57 38 5.326 IxxxxN CcchhH 27.4 9.1 214.6 6.2323026.7019e−10 0.127679 0.042173 29 30 18 4.045 KVDxK EEEeE 71.7 23.7 345.210.22337 2.3244e−24 0.207706 0.068609 81 22 1 5.808 NxV HhE 37.2 12.3189.2 7.349348 2.9702e−13 0.196617 0.064947 37 44 26 9.9 AxGF HcCC 33.511.1 222.8 6.917099 6.7617e−12 0.150359 0.049674 39 40 32 6.281 VxxxxVEcceeE 36.6 12.1 520 7.116802 1.5683e−12 0.070385 0.023302 36 40 2810.501 DxAxxD ChHhhH 28.7 9.5 168.1 6.409489 2.1528e−10 0.1707320.056547 34 38 32 4.5 DxDGxG CcCCcC 35.9 11.9 416.7 7.054973 2.4585e−120.086153 0.028573 36 39 13 4.333 TxxxxT EecceE 82.4 27.3 361.9 10.952969.5962e−28 0.227687 0.075539 88 97 64 17.615 QxxxxQ CchhhH 45.1 15 238.98.045709 1.2643e−15 0.188782 0.062644 46 53 35 8.666 DGR HCC 24.9 8.359.6 6.223041 7.9087e−10 0.417785 0.138959 28 31 21 4.046 RxxxxH HhhccC65.2 21.7 297.8 9.703437 4.3224e−22 0.218939 0.072826 71 77 61 18.915TDV CCH 28.4 9.5 124.7 6.397493 2.3547e−10 0.227747 0.075963 31 33 125.485 ExxGA HhhCC 41.1 13.7 243.7 7.613209 3.8832e−14 0.16865 0.05626848 61 43 5.717 GST CEE 28 9.3 96.7 6.422618 2.0456e−10 0.289555 0.09660728 25 8 4.048 SxxxxR CchhhH 124.8 41.7 647.7 13.30661 3.0825e−400.192682 0.064369 133 159 109 32.489 QSxxS EEccE 30.2 10.1 204.56.487393 1.2578e−10 0.147677 0.049385 37 20 3 3 AxxQG HhhHH 30.2 10.1218 6.47422 1.3671e−10 0.138532 0.046347 31 36 15 1.13 YxGS EcCC 36.112.1 183.1 7.135684 1.4043e−12 0.19716 0.06612 43 46 24 11.261 AxxGLHhhCC 41.1 13.8 280.1 7.540236 6.6990e−14 0.146733 0.049246 46 50 409.057 QxxxW HhhhH 165.8 55.6 973.5 15.20679 4.5631e−52 0.170313 0.057164158 184 121 37.643 HxxxxS HhhhcC 31.5 10.6 219.9 6.594011 6.1157e−110.143247 0.048099 34 40 30 7.333 TxAxxQ ChHhhH 35.1 11.8 204.9 6.9946513.8335e−12 0.171303 0.057525 42 42 19 4.784 TAxxxE CHhhhH 29.1 9.8 179.36.350328 3.0867e−10 0.162298 0.054574 37 31 25 1.668 MxxxxR CchhhH 51.317.3 353 8.401305 6.2683e−17 0.145326 0.048896 65 72 61 7.795 TxAQ ChHH65.5 22 303.2 9.611531 1.0400e−21 0.216029 0.072705 74 76 61 10.824 ANxPHHcC 30.6 10.3 110 6.640679 4.6760e−11 0.278182 0.093685 28 34 24 2.667YxxxM CchhH 28.1 9.5 219.6 6.178173 9.1504e−10 0.12796 0.043199 30 35 2111.567 GxxxxY CcchhH 68.3 23.1 533.9 9.630341 8.3399e−22 0.1279270.043196 66 80 46 32.127 NxxVxK CeeEeE 31.3 10.6 203.1 6.5453068.4370e−11 0.154111 0.052072 36 10 2 5.641 Dxx HhhHH 34.4 11.6 212.96.864841 9.4633e−12 0.161578 0.054645 43 43 33 1.163 NxxxN HhchH 28.59.7 69.5 6.537397 9.8303e−11 0.410072 0.138884 28 24 6 6.331 RxNG EeCC51.7 17.5 171.1 8.620737 9.9272e−18 0.302162 0.102376 46 56 34 12.172TxxDxK EeeEeE 71.3 24.2 396.7 9.891898 6.4050e−23 0.179733 0.060932 8118 2 6.808 ARxP HHcC 39.6 13.4 140.5 7.511607 8.6527e−14 0.2818510.095553 42 50 39 3.827 SxAxxA ChHhhH 31.9 10.8 324.7 6.5171789.9192e−11 0.098245 0.033327 43 44 40 8.897 LxxTG HhhHC 31.7 10.8 282.86.51068 1.0405e−10 0.112093 0.038036 35 37 21 11.255 QCG CCC 28.6 9.7138.1 6.276235 4.9829e−10 0.207096 0.070437 30 33 17 12.384 RSxxE CChhH37 12.6 179.8 7.134674 1.3888e−12 0.205784 0.070013 40 44 39 8.156 WxxxNHhhhC 95 32.4 413 11.46138 2.9542e−30 0.230024 0.078414 111 120 8019.341 FxxxR HhhhC 77.3 26.4 401.6 10.25513 1.5834e−24 0.19248 0.06569784 99 66 13.27 KVxKK EEeEE 71.2 24.3 349.6 9.858861 8.8905e−23 0.2036610.069538 81 22 1 5.808 NxAQ ChHH 32.7 11.2 137.8 6.713106 2.7429e−110.2373 0.081146 31 35 24 15.55 YxxxxE CcchhH 85.7 29.3 538.1 10.711761.2450e−26 0.159264 0.054469 95 106 83 21.141 DxxxxV EccccE 29.2 10277.5 6.186242 8.4465e−10 0.105225 0.036023 30 33 29 5.592 DxxxxW CccccE33.5 11.5 263 6.65024 4.0350e−11 0.127376 0.04362 42 41 36 8.248 DSxECChH 66 22.6 239.7 9.582583 1.3711e−21 0.275344 0.094387 64 81 50 13.344GxNxxE CcChhH 35.9 12.3 268.7 6.879201 8.2900e−12 0.133606 0.045839 3844 32 11.001 SQxxT HHhhH 29.8 10.2 148.5 6.344138 3.1629e−10 0.2006730.068853 30 38 22 5.454 RxxxxI HhhccC 47.6 16.3 347.7 7.9195293.2760e−15 0.1369 0.047007 56 60 52 10.429 IPG ECC 28.7 9.9 160 6.1794618.9798e−10 0.179375 0.061769 33 34 23 10.241 DxxxxT EccccE 70.6 24.4 5819.569481 1.4539e−21 0.121515 0.041937 79 88 58 9.906 YxxxxQ HhhhcC 40.414 300.9 7.244583 5.9055e−13 0.134264 0.046407 52 56 48 10.814 ExSG HhHC34 11.8 154.5 6.751139 2.0640e−11 0.220065 0.076071 35 44 32 6.005 SSTKHCEE 54.6 18.9 198.1 8.640682 7.9973e−18 0.275618 0.09533 65 27 1 5.536RxxxxY CcchhH 31.1 10.8 222.8 6.349861 2.9387e−10 0.139587 0.048342 4043 32 1.884 WxxxQ HhhhH 201.9 69.9 1001.1 16.36292 4.8607e−60 0.2016780.069854 204 248 166 40.546 DxAxxR ChHhhH 33.9 11.7 212.5 6.6513013.9842e−11 0.159529 0.055269 39 46 35 7 YQxxL HHhhH 40.1 13.9 386.67.155977 1.1141e−12 0.103725 0.035961 45 45 40 8.875 YxxxxR EecccC 35.912.5 301.6 6.782838 1.5881e−11 0.119032 0.041308 39 45 28 4.289 RxxGxPHhhCcC 35 12.1 274.9 6.707417 2.6783e−11 0.127319 0.044184 47 44 3911.283 VSxxE CChhH 56.4 19.6 340.2 8.573591 1.3696e−17 0.165785 0.05753961 73 52 5.783 SxxKxD HceEeE 57 19.8 313.1 8.642784 7.5321e−18 0.182050.063201 72 20 1 9.833 RxxGA HhcCC 31.8 11 222.8 6.40728 2.0139e−100.142729 0.049563 38 42 35 6.731 NxKxD CeEeE 36.1 12.5 155.1 6.9391885.5327e−12 0.232753 0.080856 43 14 2 6.641 PTE CCH 41.7 14.5 177.97.44701 1.3352e−13 0.234401 0.081576 44 40 20 7.061 TLP HCC 29.6 10.3120.5 6.286176 4.5831e−10 0.245643 0.085508 34 39 27 9 DxxGxG CccCcC95.4 33.3 1003.2 10.95388 8.3945e−28 0.095096 0.033166 90 100 43 17.791RxGL HhCC 42.9 15 220.2 7.477473 1.0395e−13 0.194823 0.067983 49 51 455.1 KxxGxN HhhCcC 32.1 11.2 196.9 6.425281 1.7880e−10 0.163027 0.05692939 43 25 4.915 QxxND HhhHH 36.3 12.7 151.8 6.922566 6.1794e−12 0.239130.083607 38 44 30 3.862 TPN CHH 40.3 14.1 123 7.419598 1.6934e−130.327642 0.114566 39 37 12 19.754 PxxxxH CcchhH 41.9 14.7 291.5 7.3029533.7793e−13 0.143739 0.050274 48 49 40 12.086 NxxRR HhhHH 32.6 11.4 160.56.512143 1.0185e−10 0.203115 0.071054 35 40 32 12.332 DVQ CHH 29.6 10.4118.8 6.257869 5.4630e−10 0.249158 0.087188 33 38 20 6.179 ExxGxP HhcCcC32.8 11.5 226.1 6.450292 1.4987e−10 0.145069 0.050838 39 40 36 2.2 QAxGHHcC 58.1 20.4 220.9 8.766703 2.5643e−18 0.263015 0.092292 61 73 5112.929 PExxN HHhhH 42.6 15 197.4 7.430722 1.4792e−13 0.215805 0.07581245 51 39 6.752 TxxSR HhhHH 30.7 10.8 166.3 6.270388 4.8902e−10 0.1846060.064858 32 34 26 6.98 NxxxV HhhcC 46.4 16.3 193.8 7.784519 9.6539e−150.239422 0.084169 52 56 46 6.751 SxxVS HhhHH 38.1 13.4 307.2 6.9023956.7722e−12 0.124023 0.043603 43 44 32 4.586 IxxxxQ CchhhH 31.2 11 289.56.22516 6.3449e−10 0.107772 0.037904 33 37 29 4.5 WxxxR HhhhC 44.2 15.5224 7.531965 6.7825e−14 0.197321 0.069416 55 55 38 5.651 TxVxK EeEeE106.2 37.4 568.5 11.64047 3.4471e−31 0.186807 0.065781 120 42 7 11.641GDxT CCcE 34.9 12.3 154.9 6.715037 2.5763e−11 0.225307 0.079419 35 31 1911.5 SAxG HHhC 37.8 13.3 158.5 7.005915 3.3764e−12 0.238486 0.084068 4242 30 6.643 MxxxxK CchhhH 41.1 14.5 281.9 7.178243 9.3821e−13 0.1457960.051396 46 53 43 11.993 PAxxS HHhhH 35.4 12.5 225.7 6.664198 3.5462e−110.156845 0.055384 41 45 31 3.833 SxAxxE ChHhhH 40.7 14.4 301.5 7.1120731.5082e−12 0.134992 0.047697 47 50 44 4.828 AxxAS HhhHC 33 11.7 2306.390864 2.1762e−10 0.143478 0.050877 40 43 31 3.792 QxxSR HhhHH 37.113.2 179.3 6.839369 1.0685e−11 0.206916 0.073569 34 35 29 6.433 KPxYCCcC 42.7 15.2 188.2 7.350314 2.6651e−13 0.226886 0.080837 37 50 234.761 QxxN HchH 38.1 13.6 85 7.25218 6.0503e−13 0.448235 0.159919 35 347 10.112 YxxxxR HhhccC 40.1 14.3 271.5 6.994423 3.4742e−12 0.1476980.052783 45 53 41 9.85 DxxxNG CcccCC 41.8 14.9 391.2 7.084546 1.7924e−120.106851 0.038196 40 42 19 10.25 GxTxxD CcChhH 47.3 16.9 366.4 7.5572455.3153e−14 0.129094 0.046209 55 63 38 13.246 RxxxxY HhhccC 47.4 17 288.67.611015 3.5521e−14 0.164241 0.058825 55 57 40 15.183 FxxxxA CcchhH 40.114.4 430 6.904445 6.4267e−12 0.093256 0.033416 48 45 35 5.002 NxxNAHhhHH 36.5 13.1 245.9 6.651858 3.7623e−11 0.148434 0.053217 33 37 224.333 RxxGV EccCC 36.3 13 227.8 6.632045 4.3072e−11 0.15935 0.057259 4143 9 2.271 GxxxxY CchhhH 50.8 18.3 530.6 7.746419 1.1980e−14 0.0957410.034427 57 64 39 23.548 KxxGxP HhhCcC 39.7 14.3 276 6.907485 6.3677e−120.143841 0.051742 48 51 38 7.563 DxxFA HhhHH 32.1 11.6 269 6.1796088.2368e−10 0.119331 0.042945 33 37 33 4.083 IxxxxQ CcchhH 42 15.1 3427.070283 1.9778e−12 0.122807 0.044214 39 45 26 4.92 PGxxE CChhH 48.517.5 230.5 7.72459 1.4791e−14 0.210412 0.07577 48 56 43 11.467 KVDK EEEE99.7 35.9 374.1 11.1934 5.8880e−29 0.266506 0.096012 109 34 1 10.641TxxxxY CcchhH 36.8 13.3 315.3 6.590914 5.5645e−11 0.116714 0.042141 4747 37 7.79 KxxxxY CcchhH 48.4 17.5 296.3 7.622571 3.2081e−14 0.1633480.059004 51 54 40 23.023 DxP EhH 32.2 11.6 75.8 6.55045 8.2319e−110.424802 0.153554 35 30 13 3.667 DxxE EhhH 85.6 30.9 287.7 10.398943.3866e−25 0.297532 0.107574 93 100 54 25.308 AAxxG HHhhC 61.5 22.3619.8 8.471116 3.0525e−17 0.099226 0.035912 73 79 69 15.583 SFT EEE 35.913 322.2 6.484796 1.1250e−10 0.111421 0.04034 43 44 40 4.286 PExxT HHhhH42.2 15.3 228.7 7.116551 1.4320e−12 0.184521 0.066926 48 42 28 6.5SxTxxD HcEeeE 58.2 21.1 334.4 8.334126 1.0029e−16 0.174043 0.063172 7420 1 10.833 YxxxQ HhhhC 102 37.1 412.9 11.16651 7.8027e−29 0.2470330.089869 111 130 98 26.582 KxxGxD HhcCcC 46.7 17 284.7 7.4153081.5458e−13 0.164032 0.059814 58 56 37 7.429 GLxP CCcH 48.9 17.8 319.37.570949 4.6990e−14 0.153148 0.055852 54 59 47 11.95 GxxxxQ CchhhH 65.423.9 462.5 8.714553 3.6676e−18 0.141405 0.05169 66 77 57 10.766 STA CHH36.2 13.2 133.8 6.648716 3.9121e−11 0.270553 0.098935 39 40 33 3.125TKVD EEEE 98.5 36 385.6 10.93326 1.0444e−27 0.255446 0.093416 111 34 211.641 IxxxQ CchhH 160.4 58.7 884.1 13.74543 6.8834e−43 0.181427 0.06636158 176 113 39.776 VxxxxE EcchhH 59.9 21.9 499.1 8.298175 1.3176e−160.120016 0.04391 66 80 34 11.21 KSR CCH 35.5 13 108.5 6.6559613.8052e−11 0.327189 0.119737 38 31 11 7.78 YxxxT HhhhC 53.2 19.5 299.77.889466 3.8511e−15 0.177511 0.06509 57 61 45 12.654 DRxG HHhC 37.3 13.7145.5 6.710008 2.5502e−11 0.256357 0.094011 42 48 40 5.333 HxxxxP HhhccC39.5 14.5 244.4 6.775202 1.5709e−11 0.16162 0.059279 39 40 31 10.047MxxxxE HhhccC 34.2 12.5 291.7 6.249721 5.1266e−10 0.117244 0.043007 4244 34 6.241 CxxxN HhhhC 35 12.8 213.2 6.379588 2.2496e−10 0.1641650.060223 37 37 21 10.833 ERxG HHcC 76.1 28 265.7 9.603856 1.0100e−210.286413 0.105454 79 91 68 16.416 LxxxE EehhH 67.4 24.8 495.9 8.7593292.4343e−18 0.135914 0.050103 75 77 37 7.941 NSG ECC 33.8 12.5 139.36.33532 3.0683e−10 0.242642 0.08945 41 36 13 7.933 GxTxY CcEeE 52.6 19.4391 7.732901 1.3037e−14 0.134527 0.04961 58 58 25 16.729 TxxxxQ CchhhH45.5 16.8 336.6 7.185919 8.2803e−13 0.135175 0.049896 53 63 45 9.89KxxxxY HhhccC 67 24.7 384 8.786447 1.9357e−18 0.174479 0.06441 78 85 6516.036 WxxxH HhhhH 68.2 25.2 453.8 8.807377 1.5890e−18 0.150286 0.05557176 85 68 19.873 FxxxxE CcchhH 87.8 32.5 685.4 9.926259 3.9216e−23 0.12810.047474 108 119 97 22.741 DxSV CcCE 35.2 13.1 239.4 6.298075 3.7348e−100.147034 0.054574 33 39 26 9.027 GxDxxE CcChhH 36.8 13.7 254.3 6.4264761.6131e−10 0.144711 0.053792 41 45 34 3.92 ExxGI HhcCC 36.6 13.7 252.16.381846 2.1498e−10 0.14518 0.054187 44 50 41 4.904 YxxxM HhhhH 172.264.3 1625.2 13.71903 9.3692e−43 0.105956 0.039595 187 196 139 41.857ExLP HhCC 42.2 15.8 295.8 6.839588 9.7186e−12 0.142664 0.053319 48 51 437 LxxxxV CchhhH 90.3 33.8 1719.7 9.813784 1.1574e−22 0.052509 0.019657106 108 80 33.523 YxxxH HhhhH 163.9 61.4 985.3 13.51545 1.5489e−410.166345 0.062287 185 210 154 53.189 STxxR HHhhH 44.8 16.8 265.4 7.068811.9236e−12 0.168802 0.063213 46 43 30 13.239 TxVxxK EeEeeE 70.3 26.3562.7 8.776302 2.0407e−18 0.124933 0.046795 81 18 2 6.808 KxSxxE CcChhH34.8 13 249.7 6.189193 7.3797e−10 0.139367 0.052226 42 44 35 8.25 QxxxxIHhhhcC 36.6 13.7 262.5 6.340297 2.7931e−10 0.139429 0.052303 42 50 286.99 RSxxL HHhhH 42.8 16.1 361.8 6.827799 1.0410e−11 0.118297 0.04437743 45 33 3.5 WxxxN HhhhH 162.9 61.2 825.6 13.50641 1.7623e−41 0.1973110.074149 156 193 123 36.661 DxAxxE ChHhhH 48.7 18.3 339.8 7.3049683.3650e−13 0.14332 0.053861 55 65 51 9.053 CxxxN HhhhH 40.5 15.2 374.66.602715 4.8363e−11 0.108115 0.040704 40 42 34 8.099 LIS EEE 36 13.6561.3 6.168581 8.1408e−10 0.064137 0.024159 42 25 20 6.364 LSxG HHcC39.7 15 242.9 6.598851 5.0502e−11 0.163442 0.061625 46 50 39 4.151 LSxxQCChhH 60.8 22.9 428.9 8.130612 5.1480e−16 0.141758 0.053451 72 77 5610.682 YRG ECC 44.6 16.9 163.1 7.137134 1.2043e−12 0.273452 0.103338 5450 22 6.727 NTKV CEEE 38 14.4 156.3 6.545601 7.4133e−11 0.2431220.091884 43 15 2 6.808 AQxxS HHhhH 50.4 19 360.1 7.381135 1.8871e−130.139961 0.052899 54 62 43 15.095 ISxxE CChhH 45.1 17.1 314.7 6.9750123.6776e−12 0.143311 0.05425 52 57 50 6.747 SSxxxD HCeeeE 41.2 15.6 216.66.724105 2.1591e−11 0.190212 0.072065 54 15 1 6.5 RxxGL HhhCC 41.8 15.9247.8 6.726746 2.0975e−11 0.168684 0.064055 53 59 49 11.51 HxxxW HhhhH45.1 17.1 463.5 6.884276 6.8432e−12 0.097303 0.036968 53 60 47 13.411KxxxxN CchhhH 38.6 14.7 224.6 6.463752 1.2361e−10 0.171861 0.065304 4241 22 10.588 RxxxxQ CcchhH 80.6 30.6 502.4 9.316053 1.4468e−20 0.160430.060976 85 89 65 15.642 IxxxY CchhH 38.1 14.5 319.7 6.350739 2.5454e−100.119174 0.045305 45 45 34 18.265 YxxxL HhhhC 91.7 34.9 677.5 9.8804216.0041e−23 0.135351 0.051474 107 115 93 33.564 DAxG HHhC 38.6 14.7 177.76.514124 8.9759e−11 0.21722 0.082658 44 52 39 10.682 NxxxxR CchhhH 74.628.5 442.8 8.941105 4.6087e−19 0.168473 0.064272 80 92 66 13.163 LSA CCH54 20.6 304.8 7.618303 3.0894e−14 0.177165 0.067607 58 69 47 8.75 AxxRHHhhHH 52.1 19.9 294.8 7.480402 8.9042e−14 0.17673 0.067458 52 53 27 9.9EGxP HCcC 36.9 14.1 148.4 6.390062 2.0520e−10 0.248652 0.094911 41 41 178.331 AFG HHC 43 16.4 221.9 6.81187 1.1651e−11 0.193781 0.074044 50 5942 3.041 STK CEE 101.6 38.9 261.2 10.9062 1.3949e−27 0.388974 0.148807104 57 4 8.703 ExxxSK HhhhHH 43.5 16.6 292.1 6.778914 1.4388e−110.148922 0.05698 52 56 39 9.048 GxDxxA CcChhH 41.7 16 346.5 6.5863675.2939e−11 0.120346 0.046127 46 50 31 10.654 FxxxQ CchhH 79.8 30.6 582.39.138367 7.4489e−20 0.137043 0.052546 91 90 68 7.139 GxSxxD CcChhH 5219.9 441.1 7.34755 2.3629e−13 0.117887 0.045205 63 68 51 14.451 SVY EEE38.3 14.7 601.1 6.238409 5.0979e−10 0.063717 0.024433 45 33 14 9.333SxxxH HhhhH 315.2 120.9 1433.7 18.46693 4.5899e−76 0.219851 0.084326 284367 224 65.875 RRxG HHhC 58 22.3 215.4 7.997367 1.5668e−15 0.2692660.103372 60 66 53 11.393 YxxxI HhhhC 40 15.4 401.6 6.397141 1.8383e−100.099602 0.038321 51 50 43 12.339 IxxS EccE 49.9 19.2 334.1 7.2098426.5925e−13 0.149356 0.057518 58 50 6 5.361 RxxGL HhcCC 53.5 20.6 3367.465023 9.8050e−14 0.159226 0.061435 64 73 61 6.592 NxxxQ HhhhC 82.631.9 264.1 9.579875 1.2068e−21 0.31276 0.12071 96 106 83 10.611 KxHGHhCC 42.9 16.6 163.8 6.820623 1.1077e−11 0.261905 0.101187 46 45 314.473 WxxxY HhhhH 104.8 40.6 939.3 10.30613 7.5914e−25 0.111572 0.043203108 124 78 32.422 YxxxxQ EecccC 38.3 14.8 329 6.232553 5.3126e−100.116413 0.045103 38 44 35 7.961 RxxxxQ CchhhH 39 15.1 262 6.3213923.0279e−10 0.148855 0.057753 45 46 40 12.704 RxxxxV HhhccC 60.7 23.6427.7 7.873856 3.9908e−15 0.141922 0.05507 76 75 62 13.656 MxxxR HhhhC53.5 20.8 301.5 7.445446 1.1360e−13 0.177446 0.068865 68 58 36 10.359QRG HCC 49.4 19.2 147.2 7.401983 1.6748e−13 0.335598 0.130253 53 54 398.2 SxxAA HhhHH 78.9 30.6 960.7 8.862496 8.8792e−19 0.082128 0.031889 8893 83 16.082 MxxxE CchhH 292 113.4 1275.4 17.56392 5.5301e−69 0.2289480.088946 304 324 216 51.442 LxxxQ CchhH 328 127.5 1903.8 18.382342.1159e−75 0.172287 0.066973 351 403 271 51.12 RxxxD ChhhH 36.4 14.2125.1 6.27883 4.1861e−10 0.290967 0.113143 37 45 33 6.167 SSxxS HHhhH 4517.5 264.2 6.803607 1.1954e−11 0.170326 0.066232 52 51 32 6.945 FxxxQHhhhH 322.3 125.4 2057.5 18.15157 1.4421e−73 0.156646 0.060927 325 351248 84.147 QTxxA HHhhH 38.6 15 285.6 6.251316 4.7151e−10 0.1351540.052588 40 45 31 10.029 PxN EhH 40.1 15.6 159.8 6.523918 8.2562e−110.250939 0.097705 43 47 28 14.533 LxxxxL CchhhH 154.3 60.1 2989.112.26441 1.5679e−34 0.051621 0.020122 172 187 154 49.359 LxxGA HhcCC40.9 16 451.2 6.360487 2.2876e−10 0.090647 0.035351 56 60 43 3.567 HPYCCC 40.1 15.6 184.8 6.46315 1.2178e−10 0.216991 0.084649 36 41 21 8.774AxxxxY CcchhH 41.9 16.4 400.6 6.451277 1.2660e−10 0.104593 0.040817 4547 29 12.417 KxTG HhHC 76.9 30 329 8.978773 3.2532e−19 0.233739 0.09121689 88 60 7.166 SPxxxS ECceeE 38.1 14.9 211.2 6.24142 5.0762e−10 0.1803980.070475 43 28 3 2 STxxD CEeeE 70.3 27.5 272.3 8.618319 8.1370e−180.258171 0.100879 78 26 4 8.333 ESxG HHhC 37.3 14.6 152.8 6.2514374.8643e−10 0.24411 0.095485 44 53 35 5.47 KRG HHC 39.6 15.5 122.76.553035 6.9434e−11 0.322738 0.126252 42 45 40 3 LxxxxE CchhhH 64.6 25.3535.1 8.003582 1.3751e−15 0.120725 0.047287 73 76 64 16.419 NxxP HhcH58.9 23.1 169.6 8.014526 1.3658e−15 0.347288 0.136201 57 64 28 17.097 WCCC 77.2 30.3 378.1 8.889715 7.1536e−19 0.204179 0.080088 74 86 41 16.678DxAxxA ChHhhH 40.7 16 424.8 6.30617 3.2326e−10 0.09581 0.037604 47 50 435.173 EGI HCC 38 14.9 170.6 6.252963 4.7535e−10 0.222743 0.087481 40 4621 7.513 ExxxxK EecceE 49.3 19.4 237 7.097573 1.4863e−12 0.2080170.081721 53 70 45 9.907 GxxxxS CcchhH 154.1 60.6 1208.3 12.329697.0867e−35 0.127535 0.050132 163 180 118 70.731 SxTxV HcEeE 67.5 26.5339.7 8.277657 1.4600e−16 0.198705 0.078155 84 28 1 10.869 GxxxxN CcchhH104.6 41.2 673.7 10.20739 2.0976e−24 0.155262 0.061083 120 141 79 47.325TxxxKK EeeeEE 69.9 27.5 416.3 8.363251 7.0078e−17 0.167908 0.066081 8017 1 6.808 YxY CcE 84.9 33.4 504.5 9.207153 3.8374e−20 0.168285 0.06629889 100 48 20.439 SxAE ChHH 122.9 48.4 589.8 11.16867 6.7314e−29 0.2083760.082117 133 148 101 18.512 ExGF HcCC 39.4 15.5 239.4 6.2590814.4518e−10 0.164578 0.064913 53 52 40 6.293 LTS CCH 43 17 240.7 6.5582016.2855e−11 0.178646 0.070463 44 41 21 2.257 NDG ECC 41.8 16.5 146.66.601243 4.8788e−11 0.28513 0.112713 43 47 12 10.913 NxxxxF CccccE 47.618.8 542.3 6.750994 1.6369e−11 0.087774 0.03471 49 51 33 10.371 PxxxxQCchhhH 62.2 24.6 503.6 7.77407 8.5531e−15 0.123511 0.048843 74 81 6712.837 RxxxR HhhhC 188.3 74.5 575 14.13525 2.7770e−45 0.327478 0.129536207 244 169 47.934 DxAS ChHH 45.9 18.2 275.4 6.736084 1.8618e−110.166667 0.065934 46 55 42 3.25 QSP EEC 55.5 22 358.1 7.3867431.7114e−13 0.154985 0.061328 68 47 8 3.5 RRxG HHcC 56.3 22.3 211.97.619259 3.0185e−14 0.265691 0.105141 57 66 51 12.853 LPP CCH 51 20.2286.8 7.109054 1.3390e−12 0.177824 0.070421 54 62 44 8.701 SxxxxD CchhhH41.5 16.5 299.4 6.349576 2.4419e−10 0.138611 0.054971 42 50 31 10.8NxxxxN HhhccC 60 23.8 376.7 7.661546 2.0833e−14 0.159278 0.063216 70 7764 7.58 NAxxS HHhhH 38.9 15.4 268.6 6.149912 8.7835e−10 0.1448250.057482 38 39 20 3.817 RxTG HhHC 45.1 17.9 213.7 6.711082 2.2341e−110.211044 0.083822 52 59 49 3.924 YxxxF HhhhH 151.3 60.1 2015.5 11.937218.2988e−33 0.075068 0.029833 153 168 122 51.948 VGS ECC 50.8 20.2 338.67.014581 2.6019e−12 0.15003 0.059706 52 58 33 16.101 IxxxxI CchhhH 43.817.4 992.1 6.369436 2.0703e−10 0.044149 0.017576 52 56 48 7.959 SxxVDCeeEE 71.1 28.4 311.2 8.413504 4.5859e−17 0.22847 0.091179 78 27 5 8GxxAA HhhHH 53.5 21.4 1130 7.01614 2.4760e−12 0.047345 0.018914 58 70 5517.258 MxxxH HhhhH 93 37.2 734.8 9.400986 5.9947e−21 0.126565 0.05057295 118 85 36.595 PxDQ ChHH 43.8 17.5 180.6 6.602266 4.6907e−11 0.2425250.097075 51 57 29 7.011 CG CH 66.5 26.7 303.6 8.076594 7.6058e−160.219038 0.087834 69 78 41 14.932 SxxxVD HceeEE 58.7 23.5 333.5 7.5138066.4629e−14 0.176012 0.070611 74 20 1 9.833 AxxGL HhcCC 49.9 20 437.56.834044 9.1072e−12 0.114057 0.045773 74 75 65 10.817 SSxK HCeE 57.923.2 198.2 7.653307 2.2980e−14 0.292129 0.117242 69 32 1 5.536 ExGG EeCC45.4 18.2 306.7 6.559515 6.0218e−11 0.148027 0.059455 44 49 22 6 IxxxxLCchhhH 79.6 32.1 1654.6 8.474998 2.5182e−17 0.048108 0.019383 92 98 7819.491 FPxR CCcC 41.6 16.8 246.4 6.282883 3.7211e−10 0.168831 0.06804 4437 27 15.541 KxDxK EeEeE 78.2 31.5 395.3 8.663783 5.1313e−18 0.1978240.079765 86 28 3 8.808 AxxxxQ CchhhH 57.6 23.3 448.3 7.308742 2.9604e−130.128485 0.051908 61 82 40 11.14 VxxxxR CchhhH 75.7 30.6 650.5 8.3567637.0348e−17 0.116372 0.047016 96 101 80 14.641 AxGL HcCC 79.5 32.1 539.58.617327 7.5507e−18 0.147359 0.059556 99 101 90 14.846 EFG HHC 47.2 19.1189.4 6.788653 1.2971e−11 0.249208 0.100739 55 59 41 16.85 LxxxxQ CcchhH58.5 23.7 469.2 7.336592 2.3940e−13 0.12468 0.050508 68 72 61 11.976RSxG HHcC 54.3 22 224.4 7.250022 4.7424e−13 0.241979 0.098051 60 66 476.848 YxxxxS HhhhcC 44.5 18 410.7 6.372091 2.0302e−10 0.108352 0.0439256 56 45 12.558 AxxAA HhhHC 61.6 25 435.1 7.54746 4.8688e−14 0.1415770.057408 79 83 77 14.553 YxxxN HhhhC 131.6 53.4 626.1 11.194544.8487e−29 0.21019 0.085253 138 164 107 10.14 NExxR HHhhH 68.6 27.9378.6 7.9956 1.4251e−15 0.181194 0.073776 74 84 53 12.711 YxxxY HhhhH208.5 84.9 1723.4 13.75447 5.1591e−43 0.120982 0.049272 217 240 17368.563 TxxxR HhhhC 81.7 33.3 353.9 8.818101 1.3071e−18 0.230856 0.09403893 98 74 13.874 RxxxxE HhhccC 173.9 70.9 874 12.7612 2.9847e−37 0.198970.08112 195 205 162 32.84 LxxxV CchhH 94.4 38.5 929.9 9.1987963.8794e−20 0.101516 0.041413 93 96 68 17.959 RExG HHhC 92.3 37.7 353.89.41839 5.1848e−21 0.260882 0.106451 103 113 87 24.407 VxxxxQ CcchhH56.1 22.9 488.3 7.10183 1.3279e−12 0.114888 0.046923 78 85 68 8.301ExxGL HhcCC 64.7 26.4 437.9 7.674219 1.8107e−14 0.147751 0.060392 82 8373 10.513 TPxxxK CHhhhH 42.6 17.4 322 6.202797 6.0232e−10 0.1322980.054102 49 49 34 12.211 RxxxF HhhhC 42.6 17.4 230.1 6.267413 4.0522e−100.185137 0.075788 43 51 42 5.093 RxxQ ChhH 123 50.4 388.2 10.969536.1545e−28 0.316847 0.129758 136 158 98 25.056 FxxxQ HhhhC 50.5 20.7311.9 6.783616 1.2804e−11 0.161911 0.066325 63 69 53 10.301 KDxG HHhC61.6 25.2 236 7.660531 2.0910e−14 0.261017 0.106924 64 75 50 10.466YxxxR HhhhH 507.5 207.9 2808.6 21.59003 2.4287e−103 0.180695 0.074032523 598 413 103.922 WxxxR HhhhH 205.3 84.2 1244.6 13.6702 1.6585e−420.164953 0.067642 211 254 169 61.82 KxFG HhHC 43.8 18 249.9 6.3201532.8637e−10 0.17527 0.071956 55 60 51 10.832 KxxGV HhhCC 49.3 20.3 325.66.663139 2.9074e−11 0.151413 0.062217 63 66 54 13.445 QKxG HHhC 50.320.7 190.7 6.89803 5.9432e−12 0.263765 0.108445 58 60 48 8.676 GxxxxRCchhhH 118.7 48.8 850.2 10.29793 7.7223e−25 0.139614 0.057438 126 137107 23 QExG HHhC 44.7 18.4 194.8 6.446972 1.2707e−10 0.229466 0.09440655 52 44 11.216 NxxxxK CchhhH 81.3 33.5 456 8.591494 9.3418e−18 0.1782890.073378 93 109 78 16.967 FxxxN HhhhH 179.4 73.9 1396.3 12.614981.8611e−36 0.128482 0.05291 198 228 158 40.24 AxxQS HhhHH 45.5 18.8322.8 6.35022 2.3121e−10 0.140954 0.058203 52 53 48 10.166 TEA CHH 9639.7 292.4 9.607131 8.5115e−22 0.328317 0.13583 92 114 61 11.498 YxxxTEcccE 41.1 17 171.8 6.153075 8.4367e−10 0.239232 0.099017 47 53 13 6.453TKxxK EEeeE 96 39.8 398.3 9.392073 6.4809e−21 0.241024 0.099903 109 33 411.141 AxxAA HhhHH 232.6 96.4 3380.2 14.07095 5.9399e−45 0.0688120.028524 260 292 237 37.003 ExxxF HhhhC 51.9 21.5 296.5 6.7972811.1516e−11 0.175042 0.072608 60 71 51 13.323 LSxxE CChhH 117.4 48.7851.8 10.13758 3.9929e−24 0.137826 0.057178 131 149 113 25.064 SAA CHH97.7 40.5 376.8 9.504205 2.2325e−21 0.259289 0.10758 104 111 64 12.337DxxxxQ CchhhH 68.3 28.3 458.4 7.749134 9.8809e−15 0.148997 0.061827 7986 64 16.775 EAxxxQ HHhhhH 45.2 18.8 422.8 6.237266 4.7014e−10 0.1069060.044414 47 52 42 11.095 FxN ChH 67.5 28 272.3 7.865817 4.0460e−150.247888 0.103 67 74 34 17.384 TxNG EeCC 49.7 20.7 275.2 6.6224823.8018e−11 0.180596 0.075273 51 58 42 8.901 HxxxQ HhhhH 327.4 136.51404.3 17.19861 2.9556e−66 0.233141 0.097192 328 400 272 59.385 HxxxNHhhhH 195.7 81.6 841.4 13.28816 2.9476e−40 0.232589 0.097006 204 230 15945.887 NxxxR HhhhH 648.3 270.4 2518.1 24.32263 1.2367e−130 0.2574560.107389 610 743 462 158.253 NGI CCE 49.4 20.6 260.4 6.597702 4.4957e−110.189708 0.079259 53 51 42 13.4 DKxG HHhC 59.5 24.9 228.9 7.3563532.0816e−13 0.259939 0.108634 67 74 39 13.515 SxxxxY ChhhhH 66 27.6 674.77.466487 8.5770e−14 0.097821 0.040894 75 86 69 24.58 DAxxR CHhhH 47.219.7 267.6 6.420888 1.4506e−10 0.176383 0.073777 49 43 20 16.283 HxxxYHhhhH 136.7 57.2 1013.4 10.82597 2.7198e−27 0.134892 0.056424 146 162 9452.442 SxTK HcEE 87.3 36.5 320.2 8.926379 4.8515e−19 0.272642 0.114065104 44 2 10.869 RxxxF HhccC 95.2 40 501.8 9.091054 1.0429e−19 0.1897170.079765 107 113 90 32.509 SxxAQ HhhHH 48.8 20.5 367.6 6.4209441.4190e−10 0.132753 0.05585 54 59 41 8.195 EGG ECC 45.7 19.2 174.16.394959 1.7583e−10 0.262493 0.110529 50 56 38 7.878 LxxxxY HhhccC 53.222.4 957.7 6.577507 4.8789e−11 0.05555 0.023412 58 53 45 13.611 ExTGHhHC 52.2 22 309.4 6.677412 2.5699e−11 0.168714 0.071133 61 72 54 7.579STxV CEeE 79.7 33.6 368.4 8.33438 8.3322e−17 0.216341 0.091281 88 33 66.767 GxxxL ChhhC 45.7 19.3 438.5 6.14382 8.3292e−10 0.104219 0.04402754 50 31 5.267 PxxAA HhhHH 66 27.9 816.2 7.342254 2.1476e−13 0.0808630.034173 74 82 64 11.664 YxxxQ HhhhH 376.9 159.4 2150.4 17.908931.0512e−71 0.17527 0.074107 374 436 305 111.215 DxxxxR CchhhH 136.7 58811.5 10.71836 8.6960e−27 0.168453 0.071505 143 168 128 34.131 HxH ChH49.4 21 166.4 6.637432 3.4999e−11 0.296875 0.126078 48 58 40 14.723PxxxxQ CcchhH 109.4 46.5 1083.7 9.42162 4.5216e−21 0.10095 0.042935 118135 95 24.269 SxExxR ChHhhH 62.2 26.5 481.7 7.130862 1.0256e−12 0.1291260.055033 80 87 70 14.016 SGxxxD EEeccE 50.1 21.4 292.4 6.4458 1.1982e−100.171341 0.073174 60 62 3 2 AxxAS HhhHH 77.3 33.1 862.3 7.8349174.7308e−15 0.089644 0.038384 98 95 79 12.6 AxxRR HhhHH 119 51 722.49.873794 5.5640e−23 0.164729 0.070617 129 147 115 15.089 NxxxxE CcchhH188.1 80.7 1090.7 12.43087 1.8292e−35 0.172458 0.073955 206 216 15332.263 RKxG HHhC 59.6 25.6 254 7.09804 1.3380e−12 0.234646 0.10065 67 7954 6.282 RxxxxE CchhhH 60.4 25.9 383.1 7.017736 2.3228e−12 0.1576610.067628 75 91 59 8.743 LxxxxV HhhccC 66.2 28.4 1605.3 7.154948.3081e−13 0.041238 0.017695 82 92 77 17.354 WxxxE HhhhH 212.2 91.11285.6 13.16755 1.3835e−39 0.165059 0.07084 221 251 188 46.713 QxxxNHhhhH 782.6 336.4 3046.6 25.79586 1.0406e−146 0.256877 0.110409 762 926577 115.112 YxxxxD HhhccC 49.9 21.5 413.3 6.306176 2.9083e−10 0.1207360.051916 58 62 47 19.646 PxW ChH 79.8 34.3 415 8.106427 5.4043e−160.192289 0.082693 81 103 66 17.843 AxxQD HhhHH 65.9 28.4 324.1 7.3770421.6844e−13 0.203332 0.087528 67 71 29 16.326 WPS CCC 53.8 23.2 328.96.603471 4.1321e−11 0.163576 0.070417 57 62 15 16.457 QxxxR HhhhC 139 60517.3 10.84212 2.2965e−27 0.268703 0.116033 151 185 120 21.397 QxxxxLHhhhcC 57.2 24.7 531.5 6.693205 2.1962e−11 0.10762 0.046493 73 74 6414.227 PxxxN HhhhC 62.1 26.8 260.8 7.184689 7.0636e−13 0.238113 0.10292759 74 51 15.003 GxTxxE CcChhH 54.9 23.8 506.5 6.54652 5.9175e−110.108391 0.046894 65 71 59 5 AxxRD HhhHH 77.3 33.4 420.4 7.90352.7836e−15 0.183873 0.07956 91 98 81 17.109 IxxxxE CcchhH 74.6 32.3754.4 7.611808 2.7000e−14 0.098887 0.042796 93 95 87 13.777 LTxxE CChhH100.6 43.5 866 8.87308 7.1316e−19 0.116166 0.050279 114 121 90 17.283DxxRR HhhHH 121.9 52.8 600.5 9.963409 2.2695e−23 0.202998 0.087883 141150 131 22.814 RAxxxR HHhhhH 62.9 27.3 536.8 6.997202 2.6193e−120.117176 0.050836 68 75 64 10.493 ExFG HhHC 57 24.7 365.9 6.7170611.8836e−11 0.15578 0.067613 73 82 64 7.303 HxxR HhcC 76.9 33.4 263.58.056204 8.3542e−16 0.291841 0.126735 84 94 67 23.162 ExxxY HhhhC 61.426.7 310.7 7.030848 2.1101e−12 0.197618 0.085867 71 83 64 13.696 SxQEChHH 54.8 23.8 271.3 6.647848 3.0642e−11 0.20199 0.08778 65 72 58 10.729GxxxxR CcchhH 133.1 57.9 856.2 10.24474 1.2603e−24 0.155454 0.067572 154174 129 29.99 KxxW CchH 52.9 23 222 6.582378 4.8269e−11 0.2382880.103638 58 59 26 16.589 QxxxQ HhhhC 119.4 51.9 424.3 9.99265 1.7280e−230.281405 0.122406 145 169 131 14.893 QAxxS HHhhH 58.8 25.6 440.66.767101 1.3211e−11 0.133454 0.058061 69 60 44 7.414 ExxxxY HhhccC 53.423.3 395.2 6.443766 1.1723e−10 0.135121 0.058842 68 76 65 18.62 SxSEChHH 61.7 26.9 315.1 7.001886 2.5790e−12 0.195811 0.085508 64 72 6013.789 IxxxN HhhhH 403.8 176.6 2697.7 17.68693 5.2702e−70 0.1496830.065459 446 502 358 79.725 ADG HCC 52.2 22.8 214.2 6.502539 8.1955e−110.243697 0.106591 57 62 34 3.587 FxxxC HhhhH 53 23.2 1300.9 6.2462684.0873e−10 0.040741 0.017826 59 63 47 15.836 FxxxH HhhhC 50.3 22 4316.187233 6.0903e−10 0.116705 0.051087 61 67 57 11.829 NxxxxS CcchhH 59.726.1 436.5 6.769024 1.2951e−11 0.13677 0.059891 63 71 57 21.808 ISxECChH 56.6 24.8 386.1 6.605482 3.9718e−11 0.146594 0.064198 65 62 554.591 TxxxxE CcchhH 153.7 67.3 1094.5 10.86893 1.6117e−27 0.1404290.061501 174 194 152 29.804 YxxxL HhhhH 540.6 236.8 6880.9 20.088539.0430e−90 0.078565 0.034417 570 655 461 161.173 IxxxT CchhH 78.9 34.6681.3 7.739718 9.8608e−15 0.115808 0.050735 83 86 62 31.31 QxxxD HhhhH1521.3 666.8 5548.2 35.2777 1.3372e−272 0.274197 0.120187 1434 1841 1141196.522 KxDK EeEE 103.4 45.3 400.6 9.155613 5.5926e−20 0.258113 0.113187114 39 4 10.641 SxKV CeEE 74.8 32.8 361.7 7.687742 1.5248e−14 0.2068010.090709 80 29 3 8.036 QxxAA HhhHH 119.9 52.6 1024 9.528485 1.5740e−210.11709 0.051362 138 153 120 19.495 ExxRL HhhHH 194.4 85.3 1592.412.14393 6.0904e−34 0.12208 0.053562 211 224 175 28.72 PxxH ChhH 61.727.1 261.6 7.012657 2.4020e−12 0.235856 0.103682 62 80 54 9.925 SxxQAHhhHH 53.7 23.6 382.6 6.394275 1.6075e−10 0.140355 0.0617 55 66 4613.703 LSxxE HHhhH 56.5 24.8 444.2 6.537592 6.2004e−11 0.127195 0.05592265 68 59 13 TKxxxK EEeeeE 67 29.5 480.9 7.130159 9.9543e−13 0.1393220.061317 77 18 2 5.808 QxxxxE CcchhH 111.8 49.3 708.3 9.23359 2.6009e−200.157843 0.069571 125 135 91 12.001 YxxxR HhhhC 88.3 39 494.7 8.2285051.8953e−16 0.178492 0.07881 114 123 99 13.731 SxY ChH 163.2 72.1 829.511.22067 3.2336e−29 0.196745 0.086964 159 192 116 32.32 TxAE ChHH 127.256.2 609.9 9.932803 3.0165e−23 0.208559 0.092199 139 163 100 18.244AxxxxI HhhccC 52.8 23.3 1142.1 6.160343 6.9870e−10 0.046231 0.020438 7879 68 18.502 NxxE EhhH 79.8 35.3 312.4 7.94677 1.9603e−15 0.2554420.113064 87 91 49 14.814 YPS CCC 75.2 33.3 377 7.598203 3.0137e−140.199469 0.088388 78 73 52 18.633 YxxxS HhhhC 68.2 30.2 392.2 7.1903936.4338e−13 0.173891 0.077062 77 87 68 19.096 NxxxQ HhhhH 622.8 276.12608.8 22.07021 6.1727e−108 0.23873 0.105815 600 741 460 139.721 ExxxxRCchhhH 96.4 42.8 631.6 8.492481 1.9932e−17 0.152628 0.067721 108 133 9012.676 RxxxAE HhhhHH 57.2 25.4 630.5 6.432535 1.2154e−10 0.0907220.040326 59 65 55 14.205 AExxS HHhhH 69 30.7 525.3 7.131241 9.7365e−130.131354 0.058394 79 89 71 7.484 HxxL HhhC 56.6 25.2 374.6 6.4850058.7495e−11 0.151095 0.067203 63 70 47 11.112 GxxxxE CchhhH 70.2 31.2512.7 7.194858 6.1244e−13 0.136922 0.06092 79 98 68 10.557 HxxxR HhhhH321.8 143.5 1583.7 15.60741 6.4283e−55 0.203195 0.090614 325 388 27361.605 ExxRR HhhHH 299.8 133.8 1539.6 15.02431 5.0311e−51 0.1947260.086878 327 382 294 72.254 ARxxQ HHhhH 63.9 28.5 473.6 6.8349768.0075e−12 0.134924 0.060212 67 74 52 15.525 QxxxG HhhhC 264.2 118.11288.7 14.10751 3.3809e−45 0.205013 0.091634 274 318 203 46.677 LxxxHHhhhH 363.9 162.7 3238 16.18427 6.2530e−59 0.112384 0.05025 367 465 281141.562 SPxxL ECceE 58.9 26.4 269 6.675323 2.4694e−11 0.218959 0.09796966 43 3 5 NxED ChHH 68.8 30.8 317.4 7.204843 5.8007e−13 0.2167610.097047 68 76 56 7.524 YxxxR CchhH 55.5 24.9 290.4 6.425431 1.3030e−100.191116 0.085617 59 64 49 11.822 QxxxR HhhhH 1090.8 488.7 4100.829.02094 3.6056e−185 0.265997 0.11917 1033 1295 830 179.836 IxxE EccE51.4 23 281.9 6.168465 6.8170e−10 0.182334 0.081702 58 59 43 6.574AxxxxV HhhccC 75.2 33.7 1390.6 7.236538 4.3596e−13 0.054077 0.024235 109116 95 16.603 SxxxxQ CcchhH 97.8 43.8 663.1 8.432856 3.2796e−17 0.1474890.066115 119 126 102 10.513 TxxDK EeeEE 91.2 40.9 412.9 8.2904191.1242e−16 0.220877 0.099016 103 25 2 11.391 KxxDG EccCC 71.2 31.9 339.77.29748 2.9121e−13 0.209597 0.094033 89 96 74 13.514 WxxxT HhhhH 96.543.3 984.1 8.269284 1.2892e−16 0.098059 0.043997 110 112 80 31.021RxxxxR EccccC 59.9 26.9 352.7 6.623809 3.4346e−11 0.169833 0.076235 6368 45 10.813 ExxGL HhhCC 56.2 25.2 392.3 6.371708 1.8190e−10 0.1432580.064332 65 70 61 6.371 DxxxxQ CcchhH 85.9 38.7 553.6 7.8713553.4039e−15 0.155166 0.069878 98 107 90 14.997 FxxxR HhhhH 380.5 171.42686.2 16.50728 3.1248e−61 0.14165 0.063807 403 441 312 92.055 TKxD EEeE103.5 46.7 416.7 8.823218 1.1095e−18 0.24838 0.112045 117 40 4 13.641LxxxE CchhH 488.7 220.5 3253.3 18.7016 4.6170e−78 0.150217 0.067791 535608 440 81.17 RxxxR HhhhH 1627.7 735 5837.9 35.21812 1.0581e−2710.278816 0.125905 1405 1795 1078 376.551 FxxxS HhhhH 203 91.7 2171.411.87273 1.5498e−32 0.093488 0.04224 223 240 192 43.44 ExxT EccE 55 24.9180.7 6.491457 8.6501e−11 0.304372 0.137879 54 68 36 9.01 IxxxR CchhH71.2 32.3 512.5 7.082769 1.3566e−12 0.138927 0.062944 76 87 67 18.638FxxxY HhhhH 156.2 70.9 2194.5 10.29735 6.7695e−25 0.071178 0.03231 176182 141 69.566 YxxxxK EecccC 59.1 26.8 527.3 6.393258 1.5451e−10 0.112080.050891 65 70 51 15.317 QxxxQ HhhhH 1076.2 488.7 4171 28.285695.1236e−176 0.25802 0.117162 997 1232 812 173.938 RxxxxL HhhccC 95.243.3 774.6 8.128103 4.1443e−16 0.122902 0.055843 114 129 103 14.173NxxxxQ CcchhH 89.8 40.8 601.9 7.943062 1.8903e−15 0.149194 0.0678 99 10983 27.066 AxxAQ HhhHH 79.5 36.2 761.4 7.381135 1.4828e−13 0.1044130.04751 84 92 74 11.5 SxM ChH 80.7 36.8 401.4 7.605818 2.7538e−140.201046 0.09156 79 91 63 19.888 VGG ECC 71.2 32.4 623.7 6.9893022.6159e−12 0.114157 0.052013 85 99 59 13.694 MxxxN HhhhH 155.3 70.81069.5 10.40015 2.3558e−25 0.145208 0.066161 170 189 149 41.172 HxxxxDCcchhH 56.9 25.9 444.9 6.267277 3.4999e−10 0.127894 0.058283 64 69 4213.693 PxG HhC 90.2 41.1 292 8.254118 1.5418e−16 0.308904 0.140865 87103 72 16.132 RxxxxL HhhhcC 87.5 39.9 702.4 7.752774 8.5135e−15 0.1245730.056842 107 115 88 22.073 SLxxE HHhhH 67.4 30.8 603.2 6.7785561.1465e−11 0.111737 0.051012 71 76 58 13.349 TxxQ EhhH 58.8 26.9 230.16.560384 5.3148e−11 0.255541 0.116691 61 71 49 12.494 QxxDA HhhHH 63.629.1 395.9 6.658707 2.6485e−11 0.160647 0.073381 67 69 46 14.471 FxxxNHhhhC 91 41.6 668.6 7.907795 2.4834e−15 0.136105 0.062228 104 116 9217.061 QxxxxP HhhccC 70.8 32.4 471.6 6.990638 2.6072e−12 0.1501270.068702 88 89 70 11.521 SPxS ECcE 55.3 25.3 221.9 6.331376 2.3956e−100.249211 0.114087 62 38 7 4 QxxxH HhhhH 270.5 123.8 1263.5 13.87558.6154e−44 0.214088 0.098019 276 333 215 63.926 NxxQ ChhH 332 152.11273.8 15.54405 1.7117e−54 0.260637 0.11941 328 391 253 68.333 ExxxAEHhhhHH 82.6 37.8 768.2 7.460296 8.0982e−14 0.107524 0.049269 90 97 8215.236 WxR EcC 53.9 24.7 209.1 6.256836 3.8814e−10 0.257771 0.11812 5364 36 20.081 HxxxE HhhhH 519.1 238.2 2247.4 19.25348 1.2780e−82 0.2309780.10597 518 620 389 108.313 AxxLQ HhhHH 64.5 29.6 881.6 6.5244336.3403e−11 0.073162 0.033578 62 57 47 5.807 NTK CEE 60.7 27.9 192.96.723444 1.7833e−11 0.314671 0.144478 65 35 7 7.334 YxxxxG EecccC 128.559.1 1454.7 9.226183 2.6007e−20 0.088334 0.040595 147 156 100 35.882DxxxxR CcchhH 80.6 37.1 502.2 7.433222 1.0069e−13 0.160494 0.073783 94110 77 21.917 VDKK EEEE 78.6 36.1 374.6 7.42806 1.0634e−13 0.2098240.0965 90 26 1 8.308 SxxxxE CcchhH 192.1 88.4 1305.4 11.42485 2.9571e−300.147158 0.06771 218 247 163 34.29 NxF ChH 105.6 48.6 612.6 8.5174711.5500e−17 0.17238 0.079361 111 102 68 30.672 PxxxxR CchhhH 112.2 51.7866.2 8.68564 3.5307e−18 0.129531 0.059641 127 145 107 30.249 SxAD ChHH93.1 42.9 534.3 7.998864 1.1948e−15 0.174247 0.080239 105 105 80 26.811ExxxR HhhhH 3545.7 1634.5 12751.1 50.62821 0.0000e+00 0.27807 0.1281873009 4163 2328 605.848 RxxV HhhC 93.3 43 530.2 7.995811 1.2235e−150.175971 0.08115 104 114 95 19.625 RxxxQ HhhhC 158.8 73.3 541.1 10.746956.0389e−27 0.293476 0.135401 191 217 149 24.372 RxxDG EccCC 67.2 31359.2 6.792614 1.0513e−11 0.187082 0.086392 84 88 64 12.849 TxxxQ HhhhH624.6 288.5 2880.6 20.86151 1.1458e−96 0.21683 0.100147 598 678 467118.683 YxxxxK HhhhcC 68.3 31.5 611.7 6.718956 1.7065e−11 0.1116560.051574 78 84 69 13.984 SxxxxS CcchhH 63.2 29.2 600.9 6.4511421.0335e−10 0.105176 0.048591 69 80 60 31.067 AxxAR HhhHH 118.4 54.81244.1 8.783439 1.4619e−18 0.095169 0.044062 130 140 111 22.224 AAxxQHHhhH 100.7 46.6 848.8 8.140927 3.6432e−16 0.118638 0.054957 122 127 9932.506 AxxxxQ CcchhH 85.1 39.4 713.6 7.484263 6.6905e−14 0.1192540.055247 104 108 83 18.21 ETG HHC 74.9 34.7 331.4 7.207961 5.4644e−130.226011 0.104757 90 97 65 15.125 SxxxxL HhhhhC 67.1 31.1 827.3 6.5774824.4042e−11 0.081107 0.037604 81 85 67 22.607 YxxxS HhhhH 214.8 99.61731.9 11.88306 1.3421e−32 0.124026 0.057535 218 259 183 47.88 AxxQQHhhHH 73.7 34.2 442.5 7.033591 1.8980e−12 0.166554 0.077271 81 92 6813.121 AxxxQ HhhhC 159.9 74.2 882.2 10.39559 2.4485e−25 0.1812510.084109 186 203 140 22.602 ExxxxQ CcchhH 78.9 36.6 518.6 7.247593.9788e−13 0.15214 0.070611 92 94 83 10.679 DxxxR HhhhH 1593.6 739.86057.4 33.50368 4.1121e−246 0.263083 0.12213 1505 1906 1138 277.568 AAxGHHhC 75.4 35 497.1 7.073599 1.4144e−12 0.15168 0.070477 89 100 78 15.642FxxE ChhH 60.5 28.1 344.2 6.366639 1.8254e−10 0.17577 0.081749 69 76 6012.197 DDxxR HHhhH 61.8 28.8 348.8 6.430871 1.1980e−10 0.177179 0.08246363 72 53 15.074 IxxxQ HhhhH 400.2 186.3 3042.8 16.17444 7.0518e−590.131524 0.061226 430 478 342 81.324 TxxxxQ CcchhH 74.5 34.7 567.56.969533 2.9520e−12 0.131278 0.061168 84 93 70 13.997 RxxxL HhhhC 172.680.5 831.2 10.80681 3.0229e−27 0.207652 0.096811 213 241 190 27.718GxxxxE CcchhH 400.5 186.8 2725.7 16.19978 4.6835e−59 0.146935 0.068536454 524 390 76.391 RAxG HHcC 86.6 40.4 412 7.653312 1.8592e−14 0.2101940.09806 103 119 91 9.868 LxxxxL HhhhcC 62.6 29.2 1199.2 6.2560423.5831e−10 0.052201 0.024354 85 125 69 27.266 YRD CCC 56.6 26.4 267.96.182857 5.9939e−10 0.211273 0.098638 54 66 36 25.66 AxxxY HhhcC 58.627.4 444.2 6.164994 6.5438e−10 0.131923 0.061597 70 81 62 14.158 YxGGCcCC 59 27.6 473.8 6.172162 6.2375e−10 0.124525 0.05816 67 68 43 24.891VxxxN HhhhH 437.6 204.7 2937.8 16.8822 5.6161e−64 0.148955 0.069662 457507 342 94.476 DxxxR HhhhC 205.1 96.1 824.3 11.82542 2.7483e−32 0.2488170.116618 248 266 172 22.767 ExxxW HhhhH 249 116.7 1634.9 12.702215.3036e−37 0.152303 0.071408 257 291 212 53.883 HxN ChH 59.7 28 226.76.400861 1.4890e−10 0.263344 0.123483 63 72 55 13.091 RxxxQ HhhhH 1065.6500 4150.3 26.97253 2.9554e−160 0.256753 0.120469 1056 1312 832 186.326YxxxK HhhhH 681 320.1 3778.3 21.08821 9.4565e−99 0.18024 0.08471 729 824583 174.419 WxxxK HhhhH 195.9 92.1 1228.6 11.24863 2.1703e−29 0.159450.074949 212 249 175 30.575 FxxxL HhhhC 61.4 28.9 908.1 6.1484477.0691e−10 0.067614 0.031808 76 83 69 21.034 AxxxxL HhhhcC 82.4 38.81305.4 7.106322 1.0716e−12 0.063122 0.029722 105 110 100 18.122 TxVDEeEE 116.5 54.9 674.4 8.681155 3.6299e−18 0.172746 0.081358 128 48 1212.641 HxxxL HhhhH 353.1 166.4 3401.1 14.84586 6.6881e−50 0.1038190.048913 371 453 320 106.756 LxxxxE CcchhH 116 54.7 1020.9 8.5166011.4929e−17 0.113625 0.053595 143 148 120 17.066 LAxG HHcC 73.6 34.7547.8 6.815209 8.6277e−12 0.134356 0.0634 87 87 80 4.742 KxxGL HhcCC60.1 28.4 463.9 6.148064 7.1894e−10 0.129554 0.061156 73 75 55 7.864DxxxxR HhhccC 74.8 35.3 488.9 6.897404 4.8780e−12 0.152997 0.072239 8896 73 16.2 DxR HcC 120.8 57.1 342.9 9.241439 2.3884e−20 0.3522890.166413 120 144 93 21.057 DxxxR HhhcC 150 70.9 559.5 10.055898.2324e−24 0.268097 0.126689 176 195 100 30.026 QGQ CCC 91.8 43.4 358.47.828759 4.6739e−15 0.256138 0.121185 89 114 67 23.688 KKxG HHhC 87.741.5 381.6 7.588969 3.0299e−14 0.229822 0.108834 96 104 80 14.791 IxxxGHhhhC 159.3 75.4 1532.9 9.900532 3.7296e−23 0.103921 0.049218 182 218162 32.855 NxxL HhhC 88.6 42 577.8 7.473791 7.1427e−14 0.15334 0.072641105 115 93 24.064 AxxxxE CcchhH 148 70.1 1242.5 9.57374 9.3271e−220.119115 0.056438 182 205 160 23.239 NxxxxK CcchhH 70.7 33.5 463.46.67288 2.3023e−11 0.152568 0.072292 80 93 57 15.919 QxxxxK HhhhcC 80.938.3 526.8 7.138789 8.6346e−13 0.153569 0.072774 102 111 83 24.241 FxxxMHhhhH 130.3 61.8 2397 8.831735 9.1511e−19 0.05436 0.025775 143 153 11045.842 IxxxH HhhhH 160.2 76 1637.9 9.889877 4.1336e−23 0.097808 0.046403171 194 149 38.766 RxxxxR CchhhH 64 30.4 468 6.305957 2.6131e−100.136752 0.064928 71 80 62 21.522 SAxxA HHhhH 64.8 30.8 919.3 6.2356184.0246e−10 0.070488 0.033488 74 86 66 15.231 QxxxL HhhhC 85.3 40.7 488.97.293506 2.7633e−13 0.174473 0.083315 102 112 88 11.179 FxxxE HhhhH345.2 164.9 2494.4 14.52726 7.3232e−48 0.13839 0.066114 362 413 30377.031 AxxxxK CchhhH 65.6 31.3 553.9 6.29968 2.6877e−10 0.1184330.056587 86 96 69 13.217 SVT EEE 97.7 46.7 1097.2 7.630634 2.0807e−140.089045 0.042549 101 108 61 15.87 SxF HcC 65.2 31.2 400.3 6.3406822.0860e−10 0.162878 0.077927 85 94 69 20.586 NxxY ChhH 129.4 61.9 7138.972069 2.6554e−19 0.181487 0.086858 137 153 113 32.324 SIP CCC 122.558.7 674 8.717895 2.5843e−18 0.181751 0.087074 138 160 113 26.542 AxxxQHhhhH 1200.9 575.4 6408.2 27.32937 1.7264e−164 0.187401 0.089798 11431371 904 221.614 PxxxN HhhhH 244.4 117.2 1114.8 12.42461 1.7671e−350.219232 0.105106 247 278 190 47.738 PAxxA HHhhH 81.8 39.3 821.26.958559 3.0611e−12 0.09961 0.047803 97 107 91 17.091 NxxM ChhH 80.138.5 489.7 6.994627 2.4124e−12 0.16357 0.078538 80 103 55 23.769 ExxxRHhhhC 358.1 171.9 1395.4 15.16136 5.9193e−52 0.256629 0.123222 418 499360 54.629 PxxxR HhhhH 719.8 345.7 3048.4 21.37119 2.2826e−101 0.2361240.113393 701 862 579 114.931 KEG HHC 69.4 33.3 254.1 6.699047 1.9722e−110.273121 0.131224 76 88 50 6.688 SxM CcE 75.8 36.4 475.7 6.7892081.0209e−11 0.159344 0.076571 83 85 47 17.817 ARxxA HHhhH 122.1 58.71454.9 8.445356 2.6748e−17 0.083923 0.040353 132 144 120 20.965 LxxxxLHhhccC 97.7 47 2223.4 7.478582 6.5648e−14 0.043942 0.021131 125 146 10937.694 ExxxxS HhhccC 134.5 64.7 919.1 8.999618 2.0332e−19 0.1463390.070398 156 177 133 21.65 FxxxH HhhhH 105.8 50.9 1207.8 7.8609393.3681e−15 0.087597 0.042149 126 136 103 37.372 GxSxE CcChH 87.9 42.3619 7.264315 3.3686e−13 0.142003 0.068333 101 107 86 23.805 DxxRS HhhHH61.7 29.7 350.8 6.13944 7.5388e−10 0.175884 0.084643 77 80 61 7.371 GSVCCE 68.4 32.9 455.6 6.418609 1.2407e−10 0.150132 0.072268 78 84 5814.803 ExxxxR HhhccC 116.1 55.9 742.2 8.375368 4.9567e−17 0.1564270.075303 145 165 130 26.948 FxxxG HhhhC 124.9 60.2 1209.9 8.5553791.0397e−17 0.103232 0.049752 146 164 116 26.139 QxxxL HhhhH 851 410.17080.9 22.42827 1.8468e−111 0.120182 0.057922 853 962 660 154.311 QxxxYHhhhH 271.3 130.8 1885.2 12.73119 3.5409e−37 0.14391 0.069396 285 331221 45.473 LxF CcE 75 36.2 816.4 6.588127 3.9326e−11 0.091867 0.04438279 80 59 18.526 YxxxE CchhH 112.3 54.3 687 8.211157 1.9695e−16 0.1634640.078974 134 152 114 35.048 ExxxxK CchhhH 94.6 45.7 621.2 7.5136335.1579e−14 0.152286 0.073579 114 124 91 25.02 QxxxF HhhhH 258.4 1252416.8 12.25568 1.3787e−34 0.106918 0.051712 267 292 198 57.252 MxxxQCchhH 65.8 31.8 417.5 6.263424 3.3882e−10 0.157605 0.07625 76 87 715.183 HxxxD HhhhH 206.8 100.1 1013.9 11.22807 2.6894e−29 0.2039650.098763 207 252 176 38.725 KxGxT CcCcC 72 34.9 523.7 6.5089956.7535e−11 0.137483 0.066578 79 71 44 14.708 PxxxM HhhhH 89.5 43.3 757.87.2189 4.6432e−13 0.118105 0.057205 102 106 84 25.723 TxY ChH 85.9 41.6440.4 7.210357 5.0580e−13 0.19505 0.09453 83 95 60 11.836 RxxxN HhhhH653.6 316.9 2892.5 20.04073 2.2101e−89 0.225964 0.109571 638 758 493166.223 TxTG CcCC 114.1 55.4 731.8 8.204551 2.0652e−16 0.155917 0.075694118 130 77 56.478 NxxH HhhH 180.4 87.6 891.3 10.44351 1.4170e−250.202401 0.098269 180 217 148 36.561 YxxxE HhhhH 396.8 192.7 2422.915.32313 4.7702e−53 0.163771 0.079539 427 499 343 75.821 VxxxQ CchhH116.7 56.7 787.6 8.275504 1.1380e−16 0.148172 0.071966 132 144 11238.882 RExxL HHhhH 112.2 54.5 836.4 8.083483 5.5774e−16 0.1341460.065161 131 138 113 26.81 NxxxY HhhhH 187.1 90.9 1394.3 10.435451.5096e−25 0.134189 0.065196 196 234 161 56.034 EAxxxE HHhhhH 84.2 40.9815.1 6.93732 3.5127e−12 0.1033 0.050228 89 93 82 20.708 AxF CcE 119.358 980.5 8.293706 9.6758e−17 0.121673 0.059176 126 137 89 19.508 PExxRHHhhH 110.7 53.8 655.7 8.086699 5.4810e−16 0.168827 0.082123 126 141 10714.452 MxxxY HhhhH 108.2 52.7 1431.8 7.795767 5.5677e−15 0.0755690.036787 109 122 88 40.104 ERxG HHhC 65.2 31.7 305.7 6.27148 3.2513e−100.213281 0.103854 76 76 70 10.267 TxxxxN ChhhhH 72.2 35.2 571.7 6.4444711.0257e−10 0.12629 0.061525 94 101 81 15.818 HxxN HhhH 260.9 127.11176.7 12.56098 3.1284e−36 0.221722 0.108046 232 287 167 78.115 SxxxNChhhH 71.4 34.8 551.2 6.406584 1.3160e−10 0.129536 0.063158 82 88 5916.96 RxxxE HhhhH 2928.1 1427.8 11214.8 42.50305 0.0000e+00 0.2610920.127313 2601 3500 2041 525.598 NxxxF HhhhH 155.5 75.8 1607.2 9.3694226.3552e−21 0.096752 0.047193 161 180 140 39.768 NxxxS HhhhH 514.3 251.12512.2 17.50681 1.1392e−68 0.204721 0.099956 526 601 395 70.614 ExxRQHhhHH 149.6 73.1 886.5 9.344841 8.1784e−21 0.168754 0.082435 158 177 14121.975 NxF HhC 72.6 35.5 446 6.491726 7.5556e−11 0.16278 0.079585 82 8771 13.599 SxxxD HhhhC 98.8 48.3 457.9 7.675582 1.4860e−14 0.2157680.105553 118 132 90 12.446 VNG ECC 97.3 47.6 641 7.485467 6.3078e−140.151794 0.07427 111 127 83 24.925 HxxxT HhhhH 192.6 94.3 1244.410.53318 5.3588e−26 0.154773 0.075761 192 227 168 35.961 FxxxD CchhH109.6 53.7 851.1 7.887565 2.7037e−15 0.128775 0.063058 116 133 90 24.115NxxxN HhhhH 411.8 201.8 1933.5 15.62583 4.3487e−55 0.212982 0.104345 422490 354 80.053 ExxLS HhhHH 102.2 50.1 839.3 7.584261 2.9242e−14 0.1217680.059728 112 129 86 14.243 YxA EeC 123.8 60.8 897.4 8.374344 4.8699e−170.137954 0.067715 132 137 87 28.11 GxxxxK CcchhH 153.6 75.4 1023 9.348957.7771e−21 0.150147 0.07375 174 189 148 33.669 LSE CCH 67.5 33.2 383.76.23691 3.9711e−10 0.175919 0.086443 73 80 62 10.044 KVxK EEeE 129 63.4665.5 8.662445 4.1119e−18 0.193839 0.09526 148 68 22 13.372 AxxER HhhHH160.2 78.8 960 9.579453 8.6052e−22 0.166875 0.082033 183 187 143 28.163LxxxQ HhhhH 838.5 412.3 6031.4 21.74665 6.4761e−105 0.139022 0.068358850 997 687 139.608 NxxxG HhhhC 114.1 56.1 662.4 8.090558 5.2533e−160.172252 0.084717 131 151 116 19.267 DExxR HHhhH 151.9 74.7 886.69.330064 9.3406e−21 0.171329 0.08428 178 190 132 23.764 HxS ChH 120.659.3 487.3 8.485009 1.9520e−17 0.247486 0.121783 122 142 94 47.563RxxxxD HhhccC 174.6 85.9 1073.5 9.970399 1.8063e−23 0.162646 0.080061201 218 156 37.795 NxA ChH 528.3 260.2 2030.4 17.79765 6.6617e−710.260195 0.128165 527 651 418 107.697 RxxxM HhhhH 316.3 155.8 2095.913.3639 8.5903e−41 0.150914 0.074339 338 384 276 66.921 EAxG HHcC 82.740.7 436.1 6.903283 4.5200e−12 0.189635 0.093429 102 118 89 12.2 QxF EeE222 109.4 1489.4 11.18519 4.2124e−29 0.149053 0.073447 230 258 15359.238 NxY ChH 107.4 52.9 534.1 7.884635 2.8091e−15 0.201086 0.099131114 124 96 17.744 WxxxS HhhhH 82.7 40.8 958.5 6.709178 1.6880e−110.086281 0.042544 93 111 71 32.016 NxxD HhhC 65.7 32.5 306.6 6.169676.1279e−10 0.214286 0.105875 73 74 52 10.337 AxxxQ CchhH 130.5 64.5770.7 8.587977 7.7782e−18 0.169327 0.08367 142 151 108 16.149 PxxQ ChhH241 119.4 891.4 11.96006 5.1935e−33 0.270361 0.13393 247 296 186 41.075SxA ChH 850.1 421.1 3347.3 22.35703 9.2441e−111 0.253966 0.125812 844989 615 158.146 AAxxR HHhhH 129.8 64.3 1242.9 8.387023 4.2884e−170.104433 0.051739 151 173 118 22.819 TxA ChH 715.6 354.6 2588.8 20.639031.1060e−94 0.276422 0.13696 686 858 491 130.016 LPxE CChH 68.7 34 555.46.130691 7.5993e−10 0.123695 0.061295 83 92 77 8.37 QxxxE HhhhC 174.586.5 667.8 10.13754 3.3887e−24 0.261306 0.129565 221 243 193 32.093SxxxxR ChhhhH 261 129.5 1853.7 11.98243 3.8015e−33 0.140799 0.069857 294311 234 48.458 QxxxM HhhhH 197.5 98 1607.1 10.37229 2.8562e−25 0.1228920.060979 210 223 171 43.25 FxA CcH 93.2 46.2 622.7 7.175335 6.2867e−130.149671 0.074273 106 100 69 24.295 RRxxA HHhhH 86.1 42.7 559.3 6.9035354.4287e−12 0.153942 0.0764 93 106 88 18.855 AAG HCC 163.7 81.2 702.79.726602 2.0695e−22 0.232959 0.115625 186 217 165 35.286 RxxxH HhhhH331.8 164.7 1574.4 13.75929 3.9545e−43 0.210747 0.104616 343 393 28491.04 KAxG HHcC 86.7 43.1 434.8 7.007685 2.1431e−12 0.199402 0.099021105 123 93 12.619 SxxG EccE 85.4 42.4 515.1 6.890972 4.8521e−12 0.1657930.082335 93 101 56 16.833 NxxxL HhhhH 450.7 223.9 4154.2 15.578098.7727e−55 0.108493 0.053909 464 574 354 121.326 SxxxQ HhhhH 680.2 3383360 19.62634 8.0947e−86 0.20244 0.100596 708 826 541 113.599 VxxxECchhH 245.6 122.1 1615.1 11.61904 2.8573e−31 0.152065 0.075624 271 323228 40.287 YxxxD HhhhH 157.6 78.4 997.2 9.32088 1.0028e−20 0.1580430.078606 154 171 131 51.967 TFP CCC 67.2 33.4 373.1 6.119638 8.2482e−100.180113 0.089618 71 71 51 18.232 DxxxW HhhhH 115.7 57.6 860.6 7.9293661.9031e−15 0.134441 0.066906 129 142 113 26.428 PxN ChH 192.2 95.7 703.210.61399 2.3079e−26 0.273322 0.136083 201 242 139 32.479 TxxxG HhhhC132.9 66.2 909 8.507609 1.5359e−17 0.146205 0.072863 160 179 129 28.082MxxxR HhhhH 285.5 142.3 1901.9 12.48189 8.0946e−36 0.150113 0.074814 303360 254 58.722 WxN EeC 79.3 39.5 468.5 6.61109 3.3332e−11 0.1692640.08437 90 103 58 28.048 VxxxT CchhH 99.3 49.5 842.9 7.295684 2.5533e−130.117808 0.058726 111 125 95 29.562 ExxxxE CcchhH 191.6 95.5 1299.310.21315 1.4953e−24 0.147464 0.073517 221 231 184 34.126 AxxRA HhhHH165.8 82.7 1804.6 9.359131 6.8374e−21 0.091876 0.045813 181 196 15234.61 DxxxxP HhhccC 81.2 40.5 566.5 6.632996 2.8486e−11 0.1433360.071521 99 106 76 12 YxxxV HhhhH 261.5 130.5 3516 11.68707 1.2533e−310.074374 0.037115 270 307 224 73.847 ExxxxR HhcccC 91.4 45.6 570.57.067226 1.3740e−12 0.16021 0.079958 107 110 92 25.338 AxxQR HhhHH 7336.5 485.4 6.292274 2.7145e−10 0.150391 0.075114 83 97 75 12.836 IxxxDHhhhH 254.3 127.1 1867.9 11.69002 1.2299e−31 0.136142 0.068034 254 301218 48.416 NxxxxD CcchhH 109.2 54.6 880.8 7.633463 1.9605e−14 0.1239780.061967 124 132 101 24.306 WxxxL HhhhH 145.8 72.9 2398.9 8.6651283.7936e−18 0.060778 0.030403 161 181 139 25.481 WxxE HhhH 321.8 161.21855.3 13.24235 4.3211e−40 0.173449 0.086864 333 381 277 57.781 FPG CCC138.7 69.5 857.5 8.66519 3.8961e−18 0.161749 0.08101 145 154 109 30.1 YHEC 69.6 34.9 354.8 6.193445 5.1633e−10 0.196167 0.098282 67 80 49 14.582DxxxxE CcchhH 154.5 77.4 1117.3 9.079327 9.3679e−20 0.13828 0.069298 177204 160 36.074 QxxR ChhH 74.6 37.4 275.8 6.539894 5.5204e−11 0.2704860.135645 82 89 58 27.364 LGL HCC 74.7 37.5 580.4 6.283761 2.8353e−100.128704 0.064592 89 91 82 13.4 PGY CCC 82.9 41.6 425.5 6.7385541.3978e−11 0.19483 0.097795 88 98 77 17.918 HxxxI HhhhH 127.4 64 1572.28.093262 4.8957e−16 0.081033 0.040701 142 153 122 38.735 AExxQ HHhhH100.1 50.3 642.7 7.316766 2.1891e−13 0.155749 0.078242 106 116 92 17.982ExxAS HhhHH 78.3 39.4 631.6 6.411106 1.2354e−10 0.123971 0.062309 84 10570 21.553 DxxRQ HhhHH 84.9 42.7 458.7 6.78259 1.0263e−11 0.1850880.093078 95 101 77 17.416 ExxxF HhhcC 77.4 38.9 528.7 6.4064021.2815e−10 0.146397 0.07363 94 106 86 11.703 AExG HHhC 70.3 35.4 410.46.143817 6.9830e−10 0.171296 0.086186 85 102 80 15.625 ASG HCC 79.4 40365.1 6.610071 3.3716e−11 0.217475 0.109465 82 89 67 27.147 DAA CHH 69.434.9 328.4 6.165825 6.1475e−10 0.211328 0.10641 74 93 54 9.497 KxxxxNHhhccC 132.1 66.5 806.8 8.389233 4.2077e−17 0.163733 0.082483 155 171124 23.736 QxxxS HhhhH 623.3 314 3007.9 18.44224 5.2220e−76 0.2072210.104399 641 765 493 120.461 IxxxE HhhhH 652.2 328.6 4866.2 18.486862.2361e−76 0.134027 0.067526 672 799 570 137.019 QxxxT HhhhH 555.2 279.92775.6 17.35473 1.5715e−67 0.200029 0.100838 576 659 427 105.928 FxxxLHhhhH 426.4 215.1 9230.4 14.57674 3.2704e−48 0.046195 0.023305 463 470340 97.989 VxxxxL CchhhH 80.9 40.8 2037.1 6.338101 1.9368e−10 0.0397130.020036 101 106 82 21.898 QxxR HhhC 128.7 65 477.4 8.509002 1.5563e−170.269585 0.136064 137 156 112 23.243 TxxxY HhhhH 213.6 107.8 202210.47044 9.9480e−26 0.105638 0.053322 239 260 177 84.626 NF HC 110.155.6 503.5 7.750356 8.0006e−15 0.218669 0.110418 112 141 92 15.526 DH HC131.5 66.4 320.4 8.971856 2.7193e−19 0.410424 0.207256 129 157 11122.973 QxxER HhhHH 70.7 35.7 399.7 6.137637 7.2446e−10 0.176883 0.08932471 79 64 15.047 DAG HCC 85.4 43.1 354.4 6.866307 5.8013e−12 0.2409710.121717 98 115 78 10.867 QQxxA HHhhH 78 39.4 558.3 6.368381 1.6309e−100.13971 0.070648 86 99 69 9.346 LxxxT CchhH 95.4 48.3 871.5 6.9830182.4411e−12 0.109466 0.055369 108 117 96 28.085 QAxxD HHhhH 99.7 50.5702.9 7.189078 5.5537e−13 0.141841 0.071827 112 122 98 13.289 KxxxxRCchhhH 83.4 42.2 572.5 6.58186 3.9651e−11 0.145677 0.073771 99 107 7716.931 SxEQ ChHH 106.6 54 926.8 7.379054 1.3464e−13 0.115019 0.058249114 129 86 22.79 QxW EeE 94.4 47.9 664.8 6.985402 2.4170e−12 0.1419980.071977 94 109 66 30.429 RxxxE HhhhC 308.8 156.5 1155 13.087933.3953e−39 0.267359 0.135538 389 450 331 52.801 NxxL ChhH 281.7 142.81993.4 12.05842 1.4819e−33 0.141316 0.071657 301 341 257 59.804 IxxxRHhhhH 603.5 306 4707.3 17.58507 2.6989e−69 0.128205 0.065013 644 748 514134.938 SxxxG HhhhC 189.6 96.2 1456 9.861034 5.1865e−23 0.13022 0.066039212 252 180 40.425 ExxxQ HhhhH 1903.9 965.9 7773.1 32.25062 3.0026e−2280.244934 0.124264 1811 2315 1395 311.531 QxP EeC 114.4 58 719.8 7.7136291.0432e−14 0.158933 0.080647 133 120 52 15.896 SxxM ChhH 89.2 45.3 602.16.789937 9.5554e−12 0.148148 0.075183 94 105 82 20 SxxxL HhhcC 74.1 37.6549.3 6.158948 6.2187e−10 0.134899 0.068513 89 100 81 21.314 NPT CCC 10352.3 577.1 7.347429 1.7329e−13 0.178479 0.090661 107 117 61 12.992 GxxQChhH 163.5 83.1 829.6 9.303796 1.1657e−20 0.197083 0.100124 173 204 13830.525 NxxN ChhH 243.7 123.8 1030.3 11.48567 1.3538e−30 0.2365330.120178 252 299 180 56.967 RxxxxP HhhccC 119.3 60.6 837.7 7.8254234.2887e−15 0.142414 0.072363 156 170 129 28.616 SxQ ChH 428.7 217.8 154715.41239 1.1886e−53 0.277117 0.140817 430 513 345 65.108 ExLG HhHC 117.459.7 783.8 7.773841 6.4656e−15 0.149783 0.076139 147 151 126 22.062YxxxT HhhhH 198.7 101.1 1762.5 10.00453 1.2198e−23 0.112738 0.057336 216230 159 40.009 SEA CHH 80.7 41.1 343 6.595633 3.6965e−11 0.2352770.119681 91 100 75 13.436 SxxxR HhhhH 800.7 407.6 4098.8 20.521421.1851e−93 0.19535 0.099432 814 960 651 163.053 LxxxN HhhhC 162.3 82.71288.9 9.05616 1.1357e−19 0.125921 0.064126 188 203 159 31.187 LxxxRHhhhH 1256.2 640.3 9084.4 25.24464 1.0887e−140 0.138281 0.070486 12901519 1082 248.703 ExxR HhhH 4348.2 2217.2 15346 48.92995 0.0000e+000.283344 0.144479 3640 5115 2655 709.592 RxxxF HhhhH 272.8 139.1 2338.611.68438 1.2799e−31 0.116651 0.059496 289 325 244 64.798 ALG HHC 97.249.6 629.4 7.045039 1.5728e−12 0.154433 0.078782 124 136 105 19.697 SxDEChHH 97.5 49.7 519.2 7.121477 9.1460e−13 0.187789 0.095803 99 113 8816.819 TxxxN HhhhC 105 53.6 580 7.371169 1.4445e−13 0.181034 0.0924 127141 104 12.344 ExxxY HhhhH 629.3 321.2 3734.6 17.97894 2.4098e−720.168505 0.086016 649 764 489 132.972 RxxxxN HhcccC 81 41.4 530.96.420158 1.1549e−10 0.152571 0.077895 93 104 61 6.844 DxxxxQ ChhhhH152.3 77.8 1117.8 8.75111 1.7751e−18 0.13625 0.06963 173 184 159 30.431LxxxY HhhhH 436.4 223 6456.4 14.54017 5.5425e−48 0.067592 0.034545 424494 322 142.511 QxxC HhhH 102.3 52.3 908 7.121624 8.9199e−13 0.1126650.057601 111 114 75 26.926 PxS EhH 130.1 66.5 449.4 8.442109 2.7448e−170.289497 0.148061 139 154 54 29.149 SxxE EhhH 86.7 44.4 455.6 6.6916611.8876e−11 0.190299 0.097361 90 102 80 12.275 WxxQ HhhH 174.6 89.41173.3 9.380752 5.5115e−21 0.148811 0.076165 198 232 142 42.633 TxxxRHhhhH 665.8 341.1 3439.7 18.52247 1.1550e−76 0.193563 0.099169 684 772543 132.037 SxxQ ChhH 506 259.3 2528 16.17084 6.8893e−59 0.2001580.102577 508 612 382 71.886 QExxA HHhhH 89.4 45.8 602.2 6.6983671.7776e−11 0.148456 0.076085 101 107 86 12.412 NxxxI HhhhH 188 96.5 20239.548308 1.0890e−21 0.092931 0.04769 181 216 156 46.585 AxxDA HhhHH 99.951.3 1121.1 6.945769 3.1146e−12 0.089109 0.045761 113 123 106 17.081RxxxxE HhcccC 98.1 50.4 624.8 7.004826 2.0838e−12 0.15701 0.080687 118132 108 16.112 VxxxQ HhhhH 449.5 231 3342.8 14.89745 2.8501e−50 0.1344680.069112 470 537 380 90.195 HxxxM HhhhH 95.5 49.1 883.3 6.8143657.8684e−12 0.108117 0.055585 103 107 81 23.829 KYG HHC 97.9 50.3 426.27.139373 8.0699e−13 0.229704 0.118099 112 125 83 16.329 EExG HHhC 98.450.6 520 7.065914 1.3554e−12 0.189231 0.097369 121 145 109 15.932 NxQEcC 117.5 60.5 485.7 7.832707 4.1145e−15 0.241919 0.124557 122 138 8024.775 RxxxD HhhhH 1124.8 579.6 4662.5 24.19752 2.0224e−129 0.2412440.12432 1106 1350 903 210.134 DxY ChH 151.5 78.1 697.2 8.8185799.8907e−19 0.217298 0.11198 158 182 134 35.046 ExxxF HhccC 104.5 53.9703.6 7.170991 6.2323e−13 0.148522 0.076616 127 124 95 22.902 PxxxECchhH 317.3 163.7 1905.6 12.55449 3.1445e−36 0.166509 0.085914 345 384267 61.567 VxxxxE CcchhH 89.2 46 874.3 6.538549 5.1382e−11 0.1020240.052642 119 127 113 27.383 AQxxA HHhhH 97 50.1 1116.6 6.7886919.3146e−12 0.086871 0.044831 115 134 101 19.916 EAxxA HHhhH 202.1 104.32020.6 9.828707 6.9670e−23 0.10002 0.051634 234 262 217 31.039 MxxxDHhhhH 153.4 79.2 1113.4 8.646793 4.4054e−18 0.137776 0.071156 179 190141 37.128 NxxxT HhhhH 370.4 191.4 2062 13.58795 3.9615e−42 0.1796310.092806 377 434 297 56.147 AGP CCC 129.7 67 642.9 8.089518 5.0769e−160.201742 0.104248 135 152 92 46.054 RxxxE CchhH 240.9 124.5 1092.311.07871 1.3526e−28 0.220544 0.114007 256 294 223 48.713 QAG HCC 72.937.7 291.4 6.147215 6.8091e−10 0.250172 0.129331 81 87 67 10.542 YxxxGHhhhC 130.4 67.4 1073.6 7.92034 1.9602e−15 0.121461 0.062812 146 170 12822.109 RxxxI HhhcC 83.8 43.4 545.9 6.399601 1.3039e−10 0.153508 0.079439100 95 76 12.163 HH HC 98.4 50.9 263.6 7.406467 1.1640e−13 0.3732930.193191 111 122 97 18.524 RRxxE HHhhH 190.5 98.6 1055.7 9.7178552.1236e−22 0.180449 0.093412 196 232 157 51.463 IxxxR HhhhC 78 40.4663.7 6.108153 8.3534e−10 0.117523 0.060846 92 93 74 14.325 AxxxR HhhhH1716.6 888.8 9975.9 29.09357 3.6109e−186 0.172075 0.089093 1654 20791299 330.422 RxxAL HhhHH 97.3 50.4 1236.5 6.745354 1.2494e−11 0.078690.04076 103 117 94 25.818 VxxxE HhhhH 776.9 402.6 5432.9 19.383768.7489e−84 0.142999 0.074111 810 954 665 148.632 NxxxH HhhhH 153.4 79.5868.2 8.690635 3.0194e−18 0.176687 0.091605 158 182 134 32.63 GxW CeE139.7 72.4 765.8 8.306914 8.2462e−17 0.182424 0.09458 141 158 102 52.85IPS CCC 86.4 44.8 533.7 6.489723 7.1959e−11 0.161889 0.083976 103 120 8017.239 RxxxL HhhhH 1346.1 698.5 9345.2 25.47497 3.0835e−143 0.1440420.074742 1360 1568 1105 261.265 DxY EeE 220.1 114.3 1491.6 10.296256.0672e−25 0.14756 0.07664 237 253 156 49.973 SxxxN HhhhH 487.3 253.12480.3 15.53476 1.6921e−54 0.196468 0.102045 506 585 397 85.22 RxxxIHhccC 83 43.1 667.3 6.28049 2.7918e−10 0.124382 0.064612 113 125 10420.075 TxxxF HhhhH 143.7 74.8 2434.2 8.087854 4.9079e−16 0.0590340.030738 151 194 129 47.689 QxxID HhhHH 80.6 42 759.4 6.1353196.9812e−10 0.106136 0.055264 93 99 79 10.301 ExxR HhhC 380.1 197.91322.8 14.04151 7.4744e−45 0.287345 0.14963 420 499 318 62.185 PGP CCC141.6 73.8 708.1 8.3469 5.8862e−17 0.199972 0.104156 122 164 99 15.171QxN EeC 209.1 109.1 732.3 10.37689 2.7159e−25 0.285539 0.148994 203 23088 39.951 LxxxN HhhhH 499.1 260.5 3907.2 15.30501 5.7912e−53 0.1277390.066663 507 592 404 98.339 PxxxT HhhhH 231.4 120.8 1405 10.52925.2470e−26 0.164698 0.085959 243 272 184 40.088 DxxY ChhH 178 92.9 969.59.283777 1.3630e−20 0.1836 0.095833 206 235 171 43.716 FxxxE CchhH 122.363.9 1018.1 7.554523 3.4465e−14 0.120126 0.062721 143 163 111 22.37 RxxEChhH 293.5 153.3 1085.3 12.21994 2.0770e−34 0.270432 0.141246 316 371249 40.946 NxxxxR ChhhhH 126.6 66.1 967 7.704717 1.0776e−14 0.130920.068383 152 165 143 38.002 YxxxK HhhhC 127.5 66.6 735.6 7.8202574.3817e−15 0.173328 0.090574 160 167 125 22.017 AxxQA HhhHH 113.8 59.51177.6 7.223678 4.1184e−13 0.096637 0.05053 135 130 105 15.993 IxxxNHhhhC 91.3 47.7 775.8 6.507313 6.2714e−11 0.117685 0.06154 111 118 959.688 RxxRE HhhHH 141.4 74 828.4 8.217981 1.7164e−16 0.17069 0.089275148 167 139 40.58 DxxRA HhhHH 112.5 58.9 823.5 7.256832 3.2587e−130.136612 0.071469 136 140 120 23.245 DxxxxK CchhhH 102.7 53.7 685.96.958082 2.8484e−12 0.14973 0.07834 118 122 92 22.493 SxF CcE 155.7 81.51168.6 8.522011 1.2853e−17 0.133236 0.06974 164 189 98 30.377 ALxxEHHhhH 108.9 57 1224.1 7.032913 1.6407e−12 0.088963 0.046595 126 136 11818.344 RxxxG HhhhC 350.8 183.7 1570 13.1164 2.2241e−39 0.223439 0.117029383 456 329 66.416 FxxxD HhhhH 141.6 74.2 1121 8.097839 4.5744e−160.126316 0.066187 163 181 136 33.51 GxxxxD CcchhH 262.4 137.5 215611.00743 2.8665e−28 0.121707 0.063779 313 341 244 68.196 FxxxK HhhhH433.1 227.1 3125.6 14.19814 7.6861e−46 0.138565 0.072648 461 528 37280.455 LAxxE HHhhH 111.2 58.3 1261.6 7.088647 1.0966e−12 0.0881420.046234 119 134 110 18.25 WxxG EecC 110 57.7 703.5 7.185905 5.5069e−130.156361 0.08202 120 135 76 29.586 IxxxE CchhH 184.4 96.7 1441.89.229114 2.2271e−20 0.127896 0.067089 214 223 179 41.502 QExxR HHhhH86.7 45.5 537.5 6.388227 1.3886e−10 0.161302 0.084616 105 117 90 16.26TxxQ ChhH 610.7 320.4 2537.9 17.34901 1.6872e−67 0.240632 0.126252 622765 470 110.722 DxxxF HhhhH 233.4 122.5 2397.6 10.28331 6.7728e−250.097347 0.051102 250 276 206 65.429 YxxS HhhC 95.6 50.2 655.1 6.670782.0931e−11 0.145932 0.076611 124 131 108 13.441 KxLG HhHC 102.4 53.8672.1 6.913764 3.8864e−12 0.152358 0.080006 128 144 109 14.959 VxxxYHhhhH 206.8 108.6 3163.8 9.585411 7.3801e−22 0.065364 0.034334 215 230166 46.981 SxxxxA CcchhH 87.1 45.8 977 6.259146 3.1360e−10 0.089150.046839 109 107 75 14.869 DxxxS HhhhC 148.4 78.1 662.7 8.4749711.9691e−17 0.223932 0.117802 169 195 145 20.945 PxxxS HhhhH 340.3 1791892.8 12.66679 7.4452e−37 0.179787 0.094585 368 431 290 56.359 YxxQHhhH 398.5 209.7 2527.7 13.61767 2.5739e−42 0.157653 0.082949 422 461320 108.519 GxxxxA CcchhH 152 80 1799.4 8.235044 1.4447e−16 0.0844730.044459 171 183 138 54.309 GxH ChH 80.3 42.3 515.6 6.100545 8.7049e−100.155741 0.08202 82 102 62 19.027 QxxxI HhhhH 314.8 165.8 3351.411.86534 1.4406e−32 0.093931 0.049481 329 374 277 59.351 QxY EeE 187.698.9 1255.4 9.293234 1.2227e−20 0.149434 0.078777 177 235 142 33.071ExxxxY HhhhhC 83.5 44 817.7 6.116442 7.7550e−10 0.102116 0.053839 103108 77 31.322 NxxG HhhC 203.8 107.5 867.4 9.925044 2.7114e−23 0.2349550.123919 222 254 190 28.398 PxxxQ ChhhH 94.4 49.8 653.3 6.5770133.9291e−11 0.144497 0.076218 110 121 87 19.008 NW CE 87.6 46.2 354.56.527002 5.6617e−11 0.247109 0.13038 87 105 56 24.622 AxxAE HhhHH 133.470.4 1311.8 7.716222 9.6679e−15 0.101692 0.053677 154 159 139 22.18QxxxA HhhhH 1147.9 606.8 7180.5 22.96015 9.5018e−117 0.159864 0.0845011109 1333 879 166.872 DGS CCE 91.7 48.5 385.8 6.638838 2.6538e−110.237688 0.125656 99 91 19 9.104 TxEQ ChHH 131 69.3 722.9 7.7994285.1196e−15 0.181215 0.095827 142 171 121 24.155 RExxA HHhhH 122.1 64.6824.6 7.452817 7.4518e−14 0.148072 0.078335 134 164 119 28.012 TxxxxRChhhhH 192.4 101.8 1444.8 9.314664 9.9140e−21 0.133167 0.070455 210 243189 43.815 TxQ ChH 358.8 189.9 1213.7 13.34734 1.0422e−40 0.2956250.156445 359 457 278 57.568 QxxL ChhH 83.7 44.3 539.5 6.1751875.4110e−10 0.155144 0.082143 90 104 69 20.665 AxxxS HhhhH 815.9 4326889.2 19.07625 3.1981e−81 0.118432 0.062711 858 1020 704 150.248 YxYEeE 228.8 121.2 2218 10.05802 6.7978e−24 0.103156 0.054624 222 239 16385.831 NxxxM HhhhH 115 60.9 1093.3 7.131459 8.0001e−13 0.105186 0.055715129 146 91 26.339 NxxS ChhH 191.8 101.6 1052.4 9.413467 3.9388e−210.18225 0.096549 203 237 171 61.026 PxxxQ HhhhH 489.4 259.6 2215.515.18275 3.8046e−52 0.220898 0.117159 516 612 413 65.861 RxxxxN HhhccC89 47.2 591.1 6.340961 1.8630e−10 0.150567 0.079865 100 105 80 18.617SxxxS HhhhH 612.2 324.9 3868.8 16.65308 2.3318e−62 0.15824 0.083981 621709 477 120.508 DxxxM HhhhH 189.7 100.7 1555.5 9.171445 3.7589e−200.121954 0.064735 193 219 148 37.831 RExxxR HHhhhH 94.3 50.1 805.46.456703 8.6412e−11 0.117085 0.062155 107 122 98 21.898 MxxxV HhhhH130.6 69.3 2641.7 7.453862 7.1767e−14 0.049438 0.026251 142 155 12025.737 NxN ChH 250.9 133.3 909.1 11.0311 2.2760e−28 0.275987 0.146586260 292 201 58.012 NxY CcE 207.7 110.3 1062.5 9.790792 1.0127e−220.195482 0.10385 211 222 130 39.035 TxW EeE 104.2 55.4 881.7 6.7766439.9170e−12 0.118181 0.06281 107 120 84 28.988 QxxxE HhhhH 1661.6 884.67199.7 27.89439 2.5759e−171 0.230787 0.122866 1626 2046 1307 271.084NxxxD HhhhH 469.1 249.9 2191.3 14.73567 3.1263e−49 0.214074 0.114022 479561 383 103.469 ExxRA HhhHH 216.7 115.4 1491.6 9.81248 8.0321e−230.14528 0.07739 245 277 198 38.212 QxxG HhhC 411.9 219.5 1555.2 14.009671.1350e−44 0.264853 0.14116 472 534 404 65.505 PExxA HHhhH 127.9 68.2958.9 7.506229 4.9065e−14 0.133382 0.071091 146 162 127 23.389 AAxxAHHhhH 198.7 105.9 3428 9.15901 4.1321e−20 0.057964 0.030896 229 253 20429.278 LSxE CChH 112.6 60.1 832.4 7.032831 1.6319e−12 0.135272 0.072187126 140 103 22.548 NxxT ChhH 183.6 98 984.6 9.105281 7.0144e−20 0.1864720.099581 196 239 160 39.061 LAxxR HHhhH 94.9 50.7 1122.2 6.3470061.7464e−10 0.084566 0.045204 115 122 104 19.449 PxxR HhhC 151.1 80.8751.3 8.279371 1.0134e−16 0.201118 0.107541 175 195 150 34.249 RxxxYHhhhH 339.3 181.4 2495.4 12.17131 3.5410e−34 0.13597 0.072706 345 403290 74.106 NxxxS HhhhC 99.5 53.2 474.7 6.7313 1.3826e−11 0.2096060.112126 132 146 111 12.42 ERG HCC 94.3 50.4 359.7 6.658952 2.3048e−110.262163 0.140245 109 112 86 12.28 TxxxN HhhhH 500.1 267.6 2640.614.99574 6.3579e−51 0.189389 0.101328 526 619 420 87.708 ExxxN HhhhH1238.3 662.5 5424.4 23.87465 4.6110e−126 0.228283 0.122138 1208 1512 928223.973 SxxG HhhC 347.9 186.1 1537.7 12.6462 9.6469e−37 0.2262470.121053 386 448 311 61.527 QxxxP HhhhH 83.8 44.8 376.3 6.1990864.6927e−10 0.222695 0.119162 80 94 72 14.007 QxxR HhhH 1231.2 658.85042.5 23.91538 1.7473e−126 0.244165 0.130659 1202 1503 918 252.525HxxxV HhhhH 215.1 115.2 2170.1 9.570428 8.4493e−22 0.09912 0.053066 227314 174 79.055 PxxxD HhhhH 353.7 189.5 1593.3 12.70558 4.5110e−370.221992 0.118948 379 452 300 59.694 DxA ChH 999.6 535.7 3592.5 21.73148.6234e−105 0.278246 0.149103 966 1249 763 132.834 PxxxH HhhhH 126 67.5704.1 7.482894 5.9047e−14 0.178952 0.095911 124 135 94 21.949 GFS CCC100.2 53.7 618 6.636855 2.5936e−11 0.162136 0.086923 112 126 86 27.305ExxH HhhH 621.9 333.5 3030.1 16.73683 5.7488e−63 0.205241 0.110077 623720 476 164.84 VxxxR HhhhH 729.3 391.2 5584 17.72605 2.1028e−70 0.1306050.070058 775 877 628 153.549 NH CE 115.1 61.8 505.6 7.245883 3.5376e−130.22765 0.122134 110 125 71 57.137 ExxxS HhhhH 1260.4 676.4 5947.223.85331 7.6202e−126 0.211932 0.113731 1205 1521 959 217.551 SxS ChH515.9 277 2080.1 15.41924 1.0009e−53 0.248017 0.133156 515 629 395104.302 GxxxH HhhhH 97.2 52.2 842.6 6.433257 9.9704e−11 0.1153570.061937 105 128 93 24.109 QxxxN HhhhC 128.4 69 622.1 7.5887732.6375e−14 0.206398 0.11087 145 165 124 21.509 RxxxxE CcchhH 143.1 76.91123 7.824477 4.0696e−15 0.127427 0.068462 170 180 127 25.24 AxP HcH82.6 44.4 318.3 6.184656 5.1804e−10 0.259504 0.139426 89 108 80 13.458SxxE ChhH 1232.3 662.1 5215.8 23.71508 2.0648e−124 0.236263 0.1269451246 1512 984 208.985 WxD EeE 90.7 48.7 612.9 6.265784 2.9867e−100.147985 0.079514 90 101 68 39.123 ExxxA HhhhC 332.6 178.8 1550.912.22687 1.8204e−34 0.214456 0.115297 412 451 342 47.966 AxxxD HhhhH831.5 447.2 4633.8 19.12119 1.3547e−81 0.179442 0.0965 825 1000 633138.75 LxxxE HhhhH 1373.3 739.2 9254.6 24.31423 1.1055e−130 0.1483910.079873 1341 1609 1068 245.576 FxxxT HhhhH 146.5 78.9 2060.1 7.7671946.3018e−15 0.071113 0.038279 151 172 132 56.842 SxxxS HhhhC 130.9 70.5730.4 7.568994 3.0401e−14 0.179217 0.096515 167 178 136 22.746 KxxxxSHhhccC 110.1 59.3 783.2 6.858237 5.5792e−12 0.140577 0.075739 133 143120 23.932 KKxG HHcC 84.7 45.7 401.4 6.137295 6.8615e−10 0.2110110.11375 101 108 85 7.445 YxG EcC 388.8 209.7 2305.9 12.97474 1.3641e−380.168611 0.090928 444 471 282 104.142 NxR ChH 288.4 155.7 1067.111.50362 1.0444e−30 0.270265 0.145939 299 351 241 95.177 TxxR ChhH 169.291.4 764.8 8.674858 3.3736e−18 0.221234 0.119488 181 197 129 46.634QxxxD HhhhC 139.6 75.5 622.3 7.877462 2.7252e−15 0.224329 0.121252 167191 146 19.277 PxxxV HhhhH 137.8 74.5 1643.4 7.506602 4.7630e−140.083851 0.04533 135 150 113 41.962 SxxxN HhhhC 129.1 69.8 738.47.458508 7.0377e−14 0.174837 0.094534 143 167 126 24.018 LxxE ChhH 118.364 675.1 7.137447 7.6498e−13 0.175233 0.094773 129 151 120 23.095 SxxxAHhhhH 836.8 452.6 7696.8 18.61578 1.8805e−77 0.108721 0.058802 847 1011693 157.111 VxxxD HhhhH 249.5 135 1847.5 10.23183 1.1317e−24 0.1350470.073088 272 319 238 36.088 TxR HcC 155.6 84.2 603.3 8.385416 4.1571e−170.257915 0.139598 166 212 128 41.373 SxxxI HhhhH 210.2 113.8 3246.19.197422 2.8543e−20 0.064755 0.035062 229 263 191 55.294 QxI EeE 286.5155.2 2264.8 10.92249 7.1076e−28 0.126501 0.068519 289 334 222 58.719RxxxI HhhhH 534.3 289.5 4313.7 14.89561 2.7733e−50 0.123861 0.067113 575665 450 135.719 TKV EEE 147.9 80.2 815.1 7.963248 1.3456e−15 0.181450.098379 163 77 26 17.155 PxxQ HhhC 103.2 56 409.4 6.796772 8.7895e−120.252076 0.136685 118 126 92 20.413 DxR ChH 544.4 295.2 1961.9 15.736447.0040e−56 0.277486 0.150465 554 668 460 83.291 ExxRE HhhHH 240.2 130.31378.1 10.11552 3.7685e−24 0.174298 0.094564 265 290 224 43.827 KxxxxEHhhhcC 89.5 48.6 591.1 6.130528 6.9930e−10 0.151413 0.082166 111 120 9619.403 RxxxD CchhH 159.2 86.4 800.2 8.292371 8.9467e−17 0.19895 0.107974163 189 130 22.888 RxxxV HhhhH 506 274.6 3969.3 14.47043 1.4670e−470.127478 0.069191 534 589 412 103.446 ExxxF HhhhH 498.5 270.6 4158.314.32931 1.1281e−46 0.119881 0.065072 514 578 426 102.392 GxW CcE 181.998.7 1119.5 8.764418 1.4965e−18 0.162483 0.088199 181 213 154 55.342 QFHC 113.5 61.6 439.7 7.122281 8.7171e−13 0.258131 0.140203 123 141 9623.442 MxxxD CchhH 103.9 56.5 674.3 6.595457 3.3788e−11 0.1540860.083733 111 126 92 15.303 QxxxS HhhhC 134.1 72.9 655.1 7.6073642.2573e−14 0.204702 0.111245 169 191 145 18.473 SxN ChH 239 129.9 996.510.26369 8.3511e−25 0.239839 0.130365 248 300 185 39.767 ExxxI HhhhH758.2 412.4 6102.5 17.63348 1.0697e−69 0.124244 0.067581 799 923 676129.885 LxxxR HhhhC 145 78.9 1150.8 7.709134 9.9857e−15 0.1259990.068569 167 189 154 41.153 PxxxA HhhhH 816.8 444.6 6116.7 18.331463.6493e−75 0.133536 0.072684 847 1009 697 134.217 ExxxH HhhhH 551.1 3002737.5 15.36047 2.4145e−53 0.201315 0.109602 593 676 485 111.491 NxxRHhhH 887.4 483.2 3933.1 19.63215 6.6235e−86 0.225624 0.12286 878 1025668 165.101 DxxR HhhC 164.8 89.8 640.4 8.54263 1.0720e−17 0.2573390.140153 182 212 152 29.523 LxxxQ HhhhC 114.8 62.5 916.8 6.8479025.9099e−12 0.125218 0.068204 154 153 122 16.295 AxxRE HhhHH 138.9 75.7940.9 7.575524 2.8327e−14 0.147625 0.080452 161 186 144 21.306 NxQ ChH274.2 149.6 988.7 11.05835 1.6363e−28 0.277334 0.151307 286 338 23451.75 NxxF ChhH 101.1 55.2 919.8 6.376146 1.4250e−10 0.109915 0.05999117 125 105 16.826 MxxxE HhhhH 326.7 178.4 2165.2 11.59541 3.4291e−310.150887 0.082375 335 380 287 62.542 RxxxW HhhhH 132.1 72.2 1089.87.303532 2.2005e−13 0.121215 0.066206 140 142 113 23.636 DxxR HhhH1950.8 1065.5 7576.4 29.25448 3.1941e−188 0.257484 0.140641 1854 23241449 369.877 RxxD HhhC 173.2 94.6 764 8.632735 4.8346e−18 0.2267020.123828 178 201 123 28.849 NxxN HhhH 471.7 257.7 2067.4 14.25193.5119e−46 0.228161 0.12463 465 568 381 98.052 TxxxD HhhhH 397.4 217.11987.2 12.96478 1.5476e−38 0.19998 0.109253 415 496 340 67.131 LxxxACchhH 132.5 72.4 1419 7.243531 3.4043e−13 0.093376 0.051052 155 175 14629.062 ExxLA HhhHH 172.9 94.5 1763.6 8.285516 9.1556e−17 0.0980380.053601 196 212 171 23.309 WxG EcC 102.7 56.2 603 6.522579 5.5005e−110.170315 0.093124 109 126 91 36.57 QxxxR HhhcC 88.9 48.6 430.5 6.1287797.1237e−10 0.206504 0.112991 106 124 86 12.945 EQxxA HHhhH 117.1 64.1862.2 6.87733 4.7983e−12 0.135815 0.074365 136 154 116 23.779 RxxxKHhhhC 144.3 79 584.7 7.89474 2.3580e−15 0.246793 0.135166 181 217 16127.224 MxxxQ HhhhH 185.4 101.6 1387.6 8.640563 4.3854e−18 0.1336120.073196 197 225 159 33.442 SxxxxN ChhhhH 104.2 57.1 951.4 6.4317599.8602e−11 0.109523 0.060001 125 133 106 18.869 QxxN HhhC 139 76.2 567.17.738658 8.1377e−15 0.245107 0.134302 152 182 130 12.68 NxxA ChhH 312.9171.5 1945.5 11.30439 9.8336e−30 0.160833 0.088165 329 396 273 78.395SxxxV HhhhH 229.5 125.8 3159.2 9.431813 3.1065e−21 0.072645 0.039829 236264 188 73.259 ExW EeE 134.4 73.7 812.2 7.414472 9.6618e−14 0.1654760.090745 145 157 92 29.744 AxxxN HhhhH 512.5 281.1 3692.5 14.356177.6211e−47 0.138795 0.076137 534 649 438 86.064 RxxxN HhhhC 140.5 77.1622.6 7.716933 9.5838e−15 0.225667 0.123805 164 183 130 24.647 YPE CCC91.8 50.4 488 6.162289 5.7200e−10 0.188115 0.103238 100 112 83 19.149EExxS HHhhH 108.6 59.6 688.3 6.641035 2.4611e−11 0.15778 0.086591 112127 82 21.926 TxxxM HhhhH 152.5 83.7 2133.3 7.669962 1.3266e−14 0.0714850.039242 160 182 126 40.979 ExxxxR HhhhcC 110.3 60.6 819.7 6.6411532.4426e−11 0.134561 0.073884 136 139 121 21.653 LxS CcH 171 93.9 1159.48.298469 8.2824e−17 0.14749 0.080997 188 204 133 31.574 RExxR HHhhH 15585.2 968.1 7.921336 1.8513e−15 0.160107 0.087988 177 191 146 31.035 SxTChH 257.9 141.7 1197.1 10.3912 2.1709e−25 0.215437 0.118404 266 323 22360.37 AxxEA HhhHH 188.2 103.4 2180.2 8.538938 1.0460e−17 0.0863220.047445 224 245 202 24.32 PxxV ChhH 184.4 101.4 1437.5 8.5541639.2654e−18 0.128278 0.070517 189 215 148 33.065 ExR CeE 196.5 108 664.39.299003 1.1605e−20 0.2958 0.162652 192 229 142 63.117 GxxxS HhhhH 289.5159.2 2551.2 10.66269 1.1802e−26 0.113476 0.06241 307 350 258 47.168TxxE EhhH 206.1 113.4 865.3 9.344617 7.4132e−21 0.238183 0.131001 237251 121 20.44 QxxxP HhhcC 133.5 73.4 676.1 7.423599 9.0723e−14 0.1974560.108619 153 159 130 20.698 TGP CCC 102.8 56.6 563.3 6.483433 7.1185e−110.182496 0.100399 112 129 81 24.898 NxxE ChhH 661 364 2655.9 16.758653.9327e−63 0.24888 0.137048 683 804 530 104.308 SxxT ChhH 228.9 126.11458.1 9.579028 7.6814e−22 0.156985 0.086477 245 277 190 35.722 DxxxQHhhhH 930.8 512.8 4144.6 19.71989 1.1598e−86 0.224581 0.123724 958 1133786 146.545 RxxxxN HhhhhC 97.2 53.6 765.7 6.176601 5.1150e−10 0.1269430.069993 121 129 105 29.151 ExxxL HhhhH 1724.7 952.4 13302.4 25.973137.7159e−149 0.129653 0.071595 1714 2036 1346 325.45 SxxxxQ ChhhhH 176.997.8 1537.4 8.267115 1.0620e−16 0.115064 0.063607 215 218 163 45.171YxxxI HhhhH 181.2 100.2 3381.2 8.207699 1.7172e−16 0.05359 0.029649 209227 176 42.552 SxR ChH 317.2 175.7 1335.1 11.46073 1.6564e−30 0.2375850.131564 313 366 248 69.543 EExxR HHhhH 314.5 174.2 1989.2 11.126847.2386e−29 0.158104 0.08758 353 399 306 47.077 QxxY HhhH 320.8 177.72179.5 11.20057 3.1483e−29 0.14719 0.081535 333 398 264 75.096 KxxxFHhhhH 328.2 181.8 2569.5 11.25855 1.6248e−29 0.127729 0.070772 360 395288 57.303 ExxAA HhhHH 179.9 99.7 1794.4 8.26671 1.0592e−16 0.1002560.055555 224 250 194 27.795 SGY CCC 105.1 58.2 565.7 6.482485 7.1196e−110.185788 0.102958 112 115 69 28.239 AxxxA HhhhC 318.2 176.4 2577.611.06323 1.4602e−28 0.123448 0.06843 397 453 358 43.621 RxxxxK HhhccC99.7 55.3 673.8 6.235508 3.5171e−10 0.147967 0.082043 118 133 101 21.553AxxxA HhhhH 2239.1 1243.1 25522.9 28.96403 1.4239e−184 0.087729 0.0487051979 2515 1570 377.986 DxxxN HhhhH 594.3 330.2 2767.7 15.489773.2073e−54 0.214727 0.119292 614 755 502 85.14 KxxxxD HhcccC 159.3 88.51094.7 7.848456 3.2713e−15 0.145519 0.080853 193 202 143 24.959 AxxLAHhhHH 115.6 64.3 3480.5 6.461798 7.8277e−11 0.033214 0.018467 137 144127 20.514 QxxxL HhccC 108.8 60.5 724.2 6.486287 6.8524e−11 0.1502350.083542 127 143 117 20.405 TxxG HhhC 243.8 135.6 1055.4 9.9544311.9130e−23 0.231002 0.128472 279 356 223 35.359 PxxR HhhH 724.7 403.33049 17.17996 2.9726e−66 0.237684 0.132276 728 858 571 110.512 DAxxAHHhhH 128.3 71.5 1234 6.928395 3.2679e−12 0.103971 0.057905 153 166 13915.792 TxxE ChhH 1201.2 669 5025.4 22.09925 2.5443e−108 0.2390260.133125 1180 1477 841 166.071 HxxxK HhhhH 307.2 171.1 1546.2 11.033542.0648e−28 0.198681 0.110656 328 403 273 68.068 TxxxI HhhhH 254.2 141.64781.1 9.604289 5.7955e−22 0.053168 0.029619 269 294 224 58.776 ExxxHHhccC 125.6 70 603.3 7.072015 1.2049e−12 0.208188 0.115991 152 164 10133.629 HxY EeE 116.4 64.9 1054 6.606772 3.0212e−11 0.110436 0.061534 129152 99 42.479 SxxY ChhH 128.7 71.7 933.9 7.000372 1.9754e−12 0.1378090.07681 138 159 100 31.063 SxH ChH 103.8 57.9 491.9 6.428179 1.0206e−100.211018 0.11764 112 118 84 36.881 HxxH HhhH 144.4 80.6 873.5 7.4640916.5267e−14 0.165312 0.092235 152 172 131 40.043 TxxxA HhhhH 589.6 3296537.3 14.74006 2.7084e−49 0.09019 0.050333 586 719 479 134.41 YQ EC128.8 71.9 489.2 7.264749 2.9907e−13 0.263287 0.146984 131 153 90 23.614KVD EEE 140.3 78.3 634.6 7.478628 5.9323e−14 0.221084 0.123433 152 79 1514.974 DxxG HhhC 433.3 241.9 1739.4 13.26116 3.0841e−40 0.2491090.139082 486 577 385 81.211 AxxG HhhC 719.2 401.9 3735.5 16.753244.1779e−63 0.192531 0.107594 792 947 645 132.901 RxxxD HhhhC 158.5 88.6698.8 7.943242 1.5551e−15 0.226817 0.126824 189 210 165 39.63 DxS ChH748.1 418.8 2698 17.51035 9.5251e−69 0.277279 0.15521 787 947 603113.524 DxxxS HhhhH 723.1 404.9 3662.5 16.77093 3.1011e−63 0.1974330.110539 766 890 604 85.339 RAxxA HHhhH 103.1 57.8 1074 6.1319596.6253e−10 0.095996 0.053785 113 124 100 18.536 GLN CCC 129 72.3 760.87.013456 1.8054e−12 0.169558 0.095002 132 159 111 25.459 NxG ChH 179.9101 926.1 8.318476 6.9400e−17 0.194255 0.109052 183 215 142 55.758 SxNHcC 189.6 106.4 732.9 8.717704 2.2519e−18 0.258698 0.145238 193 209 14329.06 SxxN ChhH 188.3 105.7 1076.5 8.458003 2.1068e−17 0.174919 0.098204217 249 167 42.44 HxxR HhhH 430.4 241.7 2107.3 12.90365 3.3433e−380.204242 0.114677 460 530 368 106.265 PxGP CcCC 106.8 60 744.8 6.3070762.1915e−10 0.143394 0.080514 96 126 75 24.033 DxxS ChhH 389.9 219.11996.9 12.23393 1.5902e−34 0.195253 0.109696 439 515 367 50.824 PF EE115.2 64.7 915.2 6.507713 5.8473e−11 0.125874 0.070726 123 150 98 38.148DxxxN HhhhC 170.6 95.9 797.1 8.136831 3.1755e−16 0.214026 0.120277 192216 157 29.035 DxxxxR ChhhhH 237 133.2 1783.5 9.344319 7.0694e−210.132885 0.07471 276 303 240 48.784 LxA CcH 231.9 130.5 1826.3 9.2140222.3961e−20 0.126978 0.071445 258 280 204 51.249 AExxR HHhhH 179.1 100.81506.8 8.070792 5.3200e−16 0.118861 0.06691 205 232 179 43.419 ExF EeE256.9 144.6 1850.1 9.723236 1.8348e−22 0.138857 0.078174 265 291 20954.885 VxxxT HhhhH 299.7 168.8 3669.7 10.31987 4.3157e−25 0.0816690.045987 328 393 253 77.133 MxxxK HhhhH 312.3 175.9 2060 10.756934.2120e−27 0.151602 0.085374 342 376 280 61.438 SxQ HcC 103.6 58.4 439.26.360122 1.5890e−10 0.235883 0.132871 118 139 102 20.556 KxxxR HhhhH1011.6 569.9 4523.9 19.79197 2.7224e−87 0.223612 0.125972 1037 1244 835185.843 GFT CCC 104.1 58.7 639.9 6.224044 3.7409e−10 0.162682 0.091679116 119 70 12.583 LxxxM HhhhH 250.7 141.3 5646.8 9.315799 9.0317e−210.044397 0.02503 266 296 217 74.072 SxxxE HhhhH 986.8 556.7 5025.919.33109 2.2728e−83 0.196343 0.110765 1001 1185 801 180.213 FxxG HhhC119.4 67.4 990.8 6.56576 3.9456e−11 0.120509 0.067998 131 155 116 29.313AAxxE HHhhH 158.9 89.7 1585.3 7.528216 3.8940e−14 0.100233 0.056558 183206 146 24.986 DxxxA HhhhC 164 92.6 833.8 7.873273 2.6801e−15 0.196690.111028 203 231 171 17.346 KxxxxE CcchhH 180.8 102.1 1300.8 8.1194173.5770e−16 0.138991 0.078458 213 237 161 45.712 ExxxE HhhhH 2968.61676.2 12774.8 33.86629 1.6289e−251 0.232379 0.131213 2577 3429 1992488.767 AxxxG HhhhC 447.2 252.6 5044.8 12.5614 2.5867e−36 0.0886460.050074 538 589 468 105.023 GYS CCC 109.9 62.1 605.1 6.4007291.1963e−10 0.181623 0.10265 125 136 79 36.053 VxxxH HhhhH 143.8 81.31671.8 7.107051 8.9332e−13 0.086015 0.048628 177 191 154 30.317 YxP EeC128.5 72.7 1189.1 6.761517 1.0351e−11 0.108065 0.061101 133 144 9924.258 FxxQ HhhH 302.1 170.8 2695.6 10.37972 2.3182e−25 0.1120720.063367 323 362 272 94.274 DxQ ChH 411.3 232.6 1454.6 12.781921.6375e−37 0.282758 0.159919 430 503 326 66.463 PxxxxE CcchhH 149.8 84.81475.9 7.272421 2.6673e−13 0.101497 0.057448 174 190 151 32.295 NxxFHhhH 192.4 108.9 1955.4 8.229704 1.4145e−16 0.098394 0.055709 197 227159 41.112 KxxxG HhhhC 339.7 192.3 1593.3 11.33192 7.0668e−30 0.2132050.120714 385 430 297 56.247 TxxxS HhhhH 331.2 187.6 2557.8 10.896349.0941e−28 0.129486 0.073325 363 417 288 67.112 MxxxS HhhhH 123.1 69.71368.3 6.561394 4.0179e−11 0.089966 0.050958 127 144 112 21.828 SxT HcE136.9 77.6 476 7.363809 1.4202e−13 0.287605 0.162952 152 89 10 15.595DxxxE HhhhC 108.3 61.4 472.6 6.422578 1.0479e−10 0.229158 0.129851 127143 99 30.155 KExG HHhC 110.3 62.5 581.6 6.398256 1.2154e−10 0.1896490.107478 136 145 117 18.342 YPG CCC 106.2 60.2 731.8 6.187731 4.6651e−100.145122 0.08227 120 121 81 23.496 EF HC 151.8 86.1 660.5 7.5891962.5096e−14 0.229826 0.13039 170 189 133 13.525 RxD ChH 290.3 164.7 102310.67984 9.9908e−27 0.283773 0.16104 284 353 222 49.531 NxxG EecC 130.774.2 683.8 6.949277 2.8332e−12 0.191138 0.10849 128 157 103 42.528 PxxRChhH 169.9 96.5 683.6 8.064812 5.7408e−16 0.248537 0.141143 202 229 16539.661 RxxG EecC 324 184.1 1428.3 11.04835 1.7317e−28 0.226843 0.128887327 383 243 62.915 PxxxQ CchhH 123 69.9 1169 6.551141 4.3072e−110.105218 0.059789 136 153 116 28.429 PxxxxL CchhhH 111.9 63.6 2362.36.141216 6.0977e−10 0.047369 0.026919 141 151 118 21.802 NxxxA HhhhH576.4 327.6 4736.9 14.24538 3.6065e−46 0.121683 0.069165 609 710 51799.648 LxQ CcH 123 69.9 744.9 6.668314 1.9809e−11 0.165123 0.093867 133149 110 24.111 SxxN HhhC 140 79.6 683.6 7.198864 4.6921e−13 0.2047980.116473 160 180 127 20.347 ExxxN HhhhC 264.5 150.5 1213.4 9.9312932.3526e−23 0.217983 0.124013 322 370 285 39.172 NxxD ChhH 392.2 223.31771.2 12.09121 9.0805e−34 0.221432 0.126069 395 486 316 65.36 PxH ChH116.7 66.4 517 6.603483 3.1220e−11 0.225725 0.128528 119 140 88 23.335HxxQ HhhH 282.1 160.6 1397.3 10.18639 1.7536e−24 0.201889 0.114965 289349 237 51.295 RF HC 157.1 89.5 702 7.654627 1.5033e−14 0.2237890.127447 178 211 155 21.792 SxxxE CchhH 215.2 122.7 1155.5 8.8389497.3988e−19 0.18624 0.106146 251 288 203 31.997 GxxxR HhhhH 452.9 258.23346.3 12.61114 1.3818e−36 0.135344 0.077167 493 565 420 109.722 RxY EeE321.4 183.3 2132.7 10.66632 1.1077e−26 0.150701 0.08596 342 399 27584.119 SxE ChH 1700.4 969.9 6349.9 25.48157 2.4624e−143 0.2677840.152747 1615 2108 1254 281.17 DxxF ChhH 139.7 79.7 1183.9 6.9578112.6034e−12 0.118 0.067327 157 188 138 23.423 RLxxE HHhhH 117.9 67.31249.5 6.341766 1.7026e−10 0.094358 0.053858 128 142 117 14.013 RxxRHhhC 223.6 127.7 881.5 9.180571 3.3400e−20 0.253659 0.144835 266 300 20846.926 TxY EeE 525.3 300 3697 13.5691 4.6027e−42 0.142088 0.08115 562610 309 124.673 DxxxD HhhhH 761.9 435.3 3587 16.6982 1.0362e−62 0.2124060.121362 755 883 574 158.083 AxxxP HhhhH 152 86.9 915.3 7.346631.5470e−13 0.166066 0.094898 161 180 135 29.146 RxxxxG EeeecC 117.9 67.41073 6.357254 1.5436e−10 0.109879 0.062797 126 132 93 30.807 NxxxE HhhhH854.2 488.3 4085.1 17.64964 7.8447e−70 0.209101 0.11952 856 1033 697158.379 QxxxG HhhhH 228.4 130.7 1785 8.871047 5.4425e−19 0.1279550.073249 248 274 196 42.146 PxS ChH 359.8 206 1492.8 11.54334 6.1661e−310.241024 0.137984 381 461 317 54.501 NxxR ChhH 186.9 107 849.5 8.2592161.1290e−16 0.220012 0.125981 200 233 166 47.681 PxxK HhhC 134.8 77.3516.7 7.0997 9.7499e−13 0.260886 0.149511 156 183 123 25.326 YxxE HhhH584.6 335.1 3516.7 14.33068 1.0637e−46 0.166235 0.095283 614 727 494119.936 SxEE ChHH 251.6 144.3 1525.5 9.392189 4.4475e−21 0.164930.094565 287 329 244 45.032 QY HC 142.8 81.9 492.7 7.372573 1.3154e−130.289832 0.16619 166 192 141 28.461 GxxA ChhH 294.2 168.8 2531.89.988638 1.2761e−23 0.116202 0.066679 325 356 261 83.468 YxR HcC 106.861.3 540.1 6.174179 5.0968e−10 0.197741 0.113477 114 128 81 23.631 RH HC196.1 112.6 557.9 8.813158 9.7271e−19 0.351497 0.201757 209 257 13831.879 RxE ChH 511.7 293.9 1726.9 13.94985 2.4681e−44 0.296311 0.170167497 646 363 89.812 SxxQ HhhH 668.9 384.6 3261.9 15.4344 7.3145e−540.205065 0.117911 667 809 547 128.299 NxxxE CchhH 153.6 88.3 790.27.369784 1.3030e−13 0.194381 0.111774 156 207 126 35.628 RxxG HhhC 641.9369.4 2583 15.31326 4.8017e−53 0.248509 0.143024 699 815 577 129.416ERxxA HHhhH 126.2 72.6 932.1 6.543421 4.5159e−11 0.135393 0.077938 150159 133 14.687 DxxD ChhH 374.5 215.7 1824.1 11.51857 8.0950e−31 0.2053070.118228 400 447 317 54.562 RxE EeE 590.6 340.3 2432.2 14.63141.3602e−48 0.242825 0.13991 596 705 466 91.584 TxxxE HhhhH 774.7 446.44237.2 16.42699 9.2564e−61 0.182833 0.105356 784 932 643 131.967 FxF EeE150.5 86.7 3210.8 6.941401 2.8496e−12 0.046873 0.027013 158 163 119 61.3DxxxY HhhhH 276.7 159.5 2217.1 9.632198 4.3574e−22 0.124803 0.071944 302341 247 76.638 KxxxL HhhhC 140.2 80.9 780.1 6.969798 2.4051e−12 0.1797210.103656 176 196 150 17.239 TPG CCC 165 95.3 927.3 7.54283 3.4767e−140.177936 0.102732 177 222 121 37.415 GxxxD HhhhH 284.4 164.2 1944.59.799636 8.4522e−23 0.146259 0.084461 311 360 263 52.673 AxxEE HhhHH123.6 71.4 897.5 6.441339 8.8743e−11 0.137716 0.079539 128 153 11024.386 PxQ ChH 131.4 75.9 551.3 6.858192 5.3635e−12 0.238346 0.137697138 175 114 22.393 RxxxP HhhcC 272.2 157.3 1341.2 9.751274 1.3823e−220.202953 0.117281 294 324 246 46.055 AxxxF HhhhH 315.3 182.3 6139.610.00393 1.0699e−23 0.051355 0.029686 326 365 264 134.406 SxxxG HhhhH213.3 123.3 2125.3 8.349052 5.0903e−17 0.100362 0.058023 225 260 19262.971 DxxQ ChhH 408.5 236.2 1714.9 12.0727 1.1263e−33 0.238206 0.137738428 518 344 49.274 WxxS HhhH 124.5 72 1244.8 6.374403 1.3622e−100.100016 0.05784 141 157 99 38.938 GxxxQ HhhhH 268.1 155.1 2029.79.443637 2.6804e−21 0.132088 0.076405 287 315 235 38.085 RxxxR HhhcC156.4 90.5 685.1 7.43411 8.0526e−14 0.228288 0.132114 188 216 156 31.425RxxEA HhhHH 116.5 67.4 1018.4 6.184135 4.6459e−10 0.114395 0.066211 131144 117 17.344 SxG HcC 511.7 296.4 2101.8 13.49625 1.2581e−41 0.2434580.141004 562 662 462 69.467 GxxxQ ChhhH 116.1 67.2 821.3 6.2171143.7900e−10 0.141361 0.08188 131 151 94 20.811 SxxL ChhH 205.4 119 19218.180858 2.0848e−16 0.106923 0.061934 227 253 190 40.531 HxxxS HhhhH162.3 94 1134.4 7.35248 1.4535e−13 0.143071 0.082885 190 209 164 37.756ExxxL HhhhC 161.1 93.4 989.5 7.354304 1.4394e−13 0.162809 0.094439 204217 169 28.44 ExxxL HhhcC 201.6 117 1358 8.183729 2.0534e−16 0.1484540.086144 245 275 222 28.455 YxP CcH 138.4 80.3 819.9 6.821998 6.7461e−120.168801 0.097974 164 177 116 35.479 VDK EEE 120.2 69.8 507.1 6.4980366.2314e−11 0.237034 0.137624 136 56 15 13.141 SxxY HhhH 260.7 151.42441.4 9.174522 3.3449e−20 0.106783 0.062004 242 283 180 72.807 DxxYHhhH 368.3 213.9 2333.5 11.07501 1.2369e−28 0.157832 0.091673 388 427293 84.209 LxV CcH 121.5 70.6 934.1 6.301937 2.1873e−10 0.1300720.075572 137 149 116 30.831 PxY CeE 141.4 82.2 1016.8 6.8146417.0386e−12 0.139064 0.080816 149 174 119 29.862 ExxxV HhhhH 640.3 372.25604 14.38506 4.7306e−47 0.114258 0.06641 656 754 552 112.908 GxG HcC179.1 104.3 868.7 7.813594 4.2001e−15 0.20617 0.120016 192 224 16744.519 DxxxG HhhhC 155.8 90.7 892.9 7.208474 4.2423e−13 0.1744880.101604 181 201 138 20.459 SxG ChH 214 124.8 1455.8 8.356712 4.7893e−170.146998 0.085692 217 266 170 52.458 FxxxG EcccC 124.7 72.7 1449.86.254867 2.9197e−10 0.086012 0.050157 134 148 103 22.432 YxE EeC 11265.3 580.6 6.12772 6.7195e−10 0.192904 0.112536 130 151 102 22.006 KxxxNHhhhH 655.3 382.3 3149.4 14.8929 2.7551e−50 0.208071 0.121401 667 805560 144.066 NxxxxK ChhhhH 173.5 101.2 1409.7 7.454423 6.6649e−140.123076 0.071816 213 230 180 31.027 RxxxA HhhhH 1371.7 800.6 8918.121.15731 1.7498e−99 0.153811 0.089769 1345 1655 1122 268.179 QxxN HhhH542.7 316.8 2555 13.56124 5.1153e−42 0.212407 0.123988 528 641 40781.716 EExxA HHhhH 231.4 135.1 1569.7 8.663887 3.3802e−18 0.1474170.086081 272 284 230 31.482 ExxxD HhhhH 1027.9 600.3 4905.2 18.630741.3593e−77 0.209553 0.122376 1027 1223 838 210.884 NxxQ HhhH 424.5 2482082.1 11.94525 5.1603e−33 0.203881 0.11909 450 514 343 83.71 LxxxDHhhhH 439.7 256.8 3658.5 11.83281 1.9411e−32 0.120186 0.070204 493 552428 61.228 AxxxT HhhhH 535.6 313 5359.1 12.96648 1.3850e−38 0.0999420.058405 566 667 467 119.61 NxxxV HhhhH 198.5 116 2149.2 7.8700982.5918e−15 0.09236 0.053993 214 241 168 42.296 AxG HcC 1022.2 597.7 436818.6919 4.3518e−78 0.23402 0.136825 1093 1343 884 165.19 SxxxD HhhhH542.1 317.1 2830.2 13.40801 4.0538e−41 0.191541 0.112045 577 678 474109.938 NxxS HhhC 143.9 84.2 634.7 6.988096 2.1104e−12 0.226721 0.132639163 170 84 15.696 LxxxS HhhhH 425.1 248.9 5887 11.41524 2.5453e−300.07221 0.042274 453 514 374 80.723 DxxH ChhH 119.9 70.3 580.8 6.310132.0985e−10 0.206439 0.121037 148 156 136 27.653 GxxE ChhH 439 257.5 229312.00864 2.3858e−33 0.191452 0.112279 458 557 364 100.014 SxxR HhhH897.4 526.5 4584.1 17.18044 2.7728e−66 0.195764 0.114856 903 1089 733182.489 TxE ChH 1585.3 930.3 5513.1 23.55417 8.6926e−123 0.2875510.168742 1546 2023 1133 224.257 RxxQ HhhC 134.4 78.9 541.4 6.759691.0508e−11 0.248245 0.145739 156 175 137 24.893 DxxG ChhH 206.7 121.61369.1 8.085262 4.5748e−16 0.150975 0.088814 241 271 193 44.741 NxG HhC207.9 122.3 887 8.331963 5.9917e−17 0.234386 0.13792 233 274 207 47.58ExxxP HhhhH 235.1 138.4 1108 8.792455 1.0954e−18 0.212184 0.124867 248300 213 46.018 ExR HcC 208.6 122.8 704.9 8.523866 1.1834e−17 0.2959290.174169 231 270 195 25.86 ExxxS HhhhC 285.9 168.3 1380.3 9.6768942.8236e−22 0.207129 0.12191 348 362 277 39.886 TxxN ChhH 136.8 80.6770.4 6.622398 2.6275e−11 0.17757 0.104563 153 183 121 29.388 RY HC179.4 105.7 690.9 7.786927 5.2074e−15 0.259661 0.153012 192 229 15745.361 PxD ChH 394.7 232.9 1487.4 11.54793 5.7222e−31 0.265362 0.156556405 495 316 70.962 RxxR HhhH 1439.9 849.7 5869.7 21.89206 2.3219e−1060.245311 0.144767 1337 1670 1062 351.183 PxxE ChhH 403.9 238.4 1641.811.59111 3.4386e−31 0.24601 0.145223 439 526 367 84.553 RxxxS HhhhC 14082.7 696.5 6.718848 1.3667e−11 0.201005 0.118672 163 195 149 22.729 GxxNChhH 131.3 77.5 799 6.424651 9.7711e−11 0.16433 0.097048 148 159 11931.848 RxxxQ HhhcC 115 67.9 528.4 6.119902 7.0248e−10 0.217638 0.128534143 161 101 18.483 TxxxT HhhhH 302.7 178.8 2535 9.61163 5.2002e−220.119408 0.07053 322 356 271 57.629 YxxS HhhH 346.5 204.8 2705.910.30319 4.9701e−25 0.128054 0.07567 407 448 323 85.864 ExxxA HhhhH2448.2 1446.9 14973 27.6968 5.5984e−169 0.163508 0.096632 2360 2967 1770391.906 NY HC 149.3 88.3 580 7.051042 1.3429e−12 0.257414 0.152234 152175 108 37.209 LxxQ HhhH 1044.9 618.7 8365.8 17.80356 4.8141e−710.124901 0.07396 1054 1237 839 205.342 RxF EeE 260.1 154 2165 8.8682175.4042e−19 0.120139 0.071144 273 304 219 68.858 GxxxT HhhhH 198.8 117.82285 7.668973 1.2522e−14 0.087002 0.051533 220 254 188 44.775 DxS CcH196.1 116.2 853.5 7.979762 1.0971e−15 0.22976 0.136101 207 261 16529.246 ExxxT HhhcC 171.6 101.7 869.5 7.378634 1.1868e−13 0.1973550.116943 190 219 164 33.207 SxxxY HhhhH 187.1 110.9 2109.6 7.4373467.4213e−14 0.08869 0.052556 221 241 180 52.01 RxxxT HhhhH 529 313.53140.6 12.82735 8.4563e−38 0.168439 0.099825 562 637 427 124.852 RxxxGEcccC 306.9 181.9 1622.6 9.832716 6.0107e−23 0.189141 0.112123 321 376245 70.592 LxxxT HhhhH 391.1 231.9 5672.7 10.6763 9.4215e−27 0.0689440.040877 411 468 353 70.436 DxxxT HhhhH 510.9 302.9 3002.8 12.599941.5506e−36 0.170141 0.100889 520 632 440 81.259 AxxxS HhhhC 167.8 99.51431 7.09616 9.3266e−13 0.117261 0.069543 206 230 172 23.643 TxN ChH178.1 105.6 773 7.587086 2.4467e−14 0.230401 0.136666 187 207 125 44.663DxxxH HhhhH 249.3 147.9 1441.7 8.798561 1.0190e−18 0.172921 0.102605 269312 243 55.987 PxxxA CchhH 156.9 93.1 1242.7 6.870682 4.6541e−120.126257 0.074941 179 191 130 30.164 ExxQ ChhH 130.4 77.4 549 6.4998666.0311e−11 0.237523 0.140984 148 174 121 22.094 DxR EeE 241.4 143.31105.4 8.782154 1.1928e−18 0.218382 0.129651 241 273 175 55.856 VxxxGHhhhC 156.3 92.9 1639 6.779043 8.7424e−12 0.095363 0.056653 194 215 17426.154 AxxxE HhhhH 1813.4 1077.4 10751.7 23.6388 1.1253e−123 0.1686620.100207 1799 2218 1404 311.318 DxxL ChhH 415.6 247 2867.7 11.221422.3305e−29 0.144925 0.086134 474 521 401 85.252 ExxxG HhhhC 343.9 204.41996.9 10.29927 5.2066e−25 0.172217 0.102356 401 457 326 66.121 SxxRChhH 182.9 108.7 943.8 7.562349 2.9256e−14 0.193791 0.115201 190 221 17440.459 YxxR HhhH 419.1 249.3 2896.8 11.25098 1.6663e−29 0.1446770.086053 445 505 368 95.767 MxxxA HhhhH 219.1 130.3 4056.4 7.90411.9271e−15 0.054013 0.032129 233 243 178 49.827 KxxxQ HhhhH 1012.7 602.64794.5 17.86682 1.5795e−71 0.211221 0.125685 1071 1266 813 210.211 LxPCcH 462.1 275 3282.8 11.78653 3.3267e−32 0.140764 0.083772 517 589 39366.229 NxQ CcE 241.5 143.8 921.8 8.867344 5.6237e−19 0.261987 0.156009246 295 178 38.902 KxxxY HhhhH 398 237.1 2680.3 10.94733 4.9780e−280.148491 0.088449 422 490 362 82.687 AExxA HHhhH 177.1 105.6 20167.14469 6.4810e−13 0.087847 0.052392 206 232 184 27.754 QxP HcC 209.1124.7 802.5 8.222219 1.4978e−16 0.260561 0.155407 224 278 195 37.428 SLPCCC 173.3 103.4 1051.9 7.242306 3.2273e−13 0.16475 0.098276 192 223 15733.474 FxP CcH 163.8 97.7 1281.6 6.955237 2.5528e−12 0.127809 0.076247187 207 154 26.16 PxxxE HhhhH 874.8 522 4147.7 16.51668 2.0506e−610.210912 0.12585 902 1091 727 146.13 DxF ChH 126.5 75.5 775.9 6.1753814.8333e−10 0.163036 0.097325 138 154 118 25.97 DxR EcC 177.6 106.1 973.97.352718 1.4250e−13 0.18236 0.10895 180 199 138 42.006 YxxG EecC 245.6146.8 1707.4 8.533428 1.0309e−17 0.143844 0.085957 256 293 188 44.484ExxxQ HhhhC 184.1 110.1 858.5 7.555177 3.0917e−14 0.214444 0.128231 227256 207 21.363 ExxR HhcC 256.7 153.6 992.7 9.051119 1.0566e−19 0.2585880.154704 298 340 220 47.105 SxxD ChhH 740.5 443 3728.2 15.055052.3442e−51 0.198621 0.118834 773 907 609 152.565 RxxxS HhhhH 610.4 365.33531.9 13.54145 6.4805e−42 0.172825 0.103436 651 743 536 147.715 VPG CCC166.4 99.6 1134.4 7.006024 1.7808e−12 0.146685 0.087813 192 224 16628.485 KxxxE CchhH 374.5 224.2 1690.2 10.77748 3.2446e−27 0.2215710.132651 395 458 302 76.148 CS HH 163.9 98.2 1268 6.908564 3.5402e−120.129259 0.077411 171 185 97 46.169 DxN ChH 418.4 250.6 1597.8 11.545595.7935e−31 0.26186 0.156827 433 521 349 57.653 AxxR HhhH 1961.9 1175.211570.1 24.20913 1.2946e−129 0.169566 0.101576 1808 2329 1411 364.394FxxS HhhH 256.5 153.7 2817.2 8.532759 1.0219e−17 0.091048 0.054542 286316 239 65.283 QxxG HhcC 372.1 222.9 1610.9 10.76288 3.8093e−27 0.2309890.138391 426 493 371 65.685 HxxE HhhH 473.2 283.5 2266.1 12.043281.5453e−33 0.208817 0.125115 484 591 400 98.106 ExxG HhhC 927.7 556.23737.1 17.07683 1.6364e−65 0.248241 0.148819 1016 1234 849 159.494 TxxxHHhhhH 158.4 95 1225.2 6.777905 8.8108e−12 0.129285 0.077507 185 197 15838.052 LxxxD CchhH 251 150.5 3175.1 8.394641 3.3309e−17 0.0790530.047397 284 311 232 49.522 AxxxH HhhhH 353 211.8 3069.1 10.050936.5266e−24 0.115017 0.069026 373 426 305 99.698 DxxxV HhhhH 310.1 186.23011.7 9.379048 4.7618e−21 0.102965 0.06181 318 357 260 55.713 KxxxHHhhhH 282.8 169.8 1521 9.202981 2.5409e−20 0.18593 0.111622 301 362 24194.486 SxxxQ ChhhH 160.3 96.2 1237.6 6.799777 7.5620e−12 0.1295250.077763 181 204 150 36.116 QxxxA HhhhC 135.6 81.5 743.3 6.3558581.5158e−10 0.18243 0.109602 174 199 154 22.04 KxxxD HhhhH 1559.9 937.57193.2 21.79635 1.8415e−105 0.216858 0.130335 1513 2010 1131 232.776QxxI HhhH 566.2 340.5 4971.5 12.67152 6.0800e−37 0.113889 0.068494 599676 469 89.516 ExxxxP HhcccC 160.6 96.6 1356.6 6.758251 1.0039e−110.118384 0.071199 205 218 173 30.38 YxS EeE 207.4 124.8 2356 7.6034422.0554e−14 0.088031 0.052952 226 241 161 57.467 RxxEE HhhHH 141 84.8971.6 6.385644 1.2352e−10 0.145121 0.087296 162 180 143 26.819 KxxxEHhhhC 340.5 204.9 1480.5 10.20524 1.3831e−24 0.22999 0.138401 402 482329 38.586 DxxH HhhH 278.9 167.8 1432.4 9.123795 5.2948e−20 0.1947080.117174 316 366 268 57.292 PxxN HhhH 169.2 101.9 934.3 7.0646471.1733e−12 0.181098 0.109055 180 215 142 19.912 DxxR ChhH 424.4 255.71831.5 11.37574 4.0622e−30 0.231723 0.1396 442 539 373 86.94 ExxxT HhhhH863.4 520.4 5003.9 15.88451 5.8664e−57 0.172545 0.103999 893 1035 747128.695 PxxQ HhhH 457.1 275.6 2183.2 11.69472 9.9071e−32 0.2093720.126244 485 582 395 66.605 RxR CcE 174.4 105.2 662.2 7.3602251.3652e−13 0.263365 0.158821 171 202 137 45.897 AxxxM HhhhH 216.2 130.44230.4 7.627727 1.6849e−14 0.051106 0.030833 247 277 216 51.702 TxR ChH214.3 129.3 922.7 8.061588 5.5443e−16 0.232253 0.140129 214 260 17046.253 KxxxN HhhhC 184.1 111.1 842.5 7.431858 7.8583e−14 0.2185160.131881 221 255 175 34.005 NxG EcC 266.8 161.1 1531.2 8.808729.1688e−19 0.174242 0.105181 275 305 146 82.701 RxxD ChhH 233.9 141.21264 8.276139 9.2445e−17 0.185047 0.111716 254 322 222 38.672 KxxxMHhhhH 288.8 174.5 2042.3 9.05073 1.0196e−19 0.141409 0.085429 306 360253 62.497 SxxxxL ChhhhH 176.2 106.5 2832.5 6.880847 4.2026e−12 0.0622070.03761 209 220 186 45.913 ExxAR HhhHH 162.3 98.2 1479.8 6.6998941.4889e−11 0.109677 0.066333 184 208 161 27.669 QxD ChH 147.6 89.4 587.16.689422 1.6561e−11 0.251405 0.152227 151 172 107 36.91 TxEE ChHH 243.4147.4 1546.4 8.314461 6.6330e−17 0.157398 0.095312 283 303 226 41.814TxxxL HhhhH 483.5 292.8 8858.3 11.33044 6.5072e−30 0.054582 0.033058 520621 429 125.095 ExxxM HhhhH 403.4 244.3 3338.3 10.57111 2.8892e−260.12084 0.073189 443 500 359 67.95 MxxxL HhhhH 227.6 137.9 5514.67.738694 7.0433e−15 0.041272 0.025002 267 288 224 56.394 YxxD HhhH 309.6187.6 1936.7 9.372461 5.0951e−21 0.15986 0.096867 326 376 282 53.375 KYHC 311.9 189.1 1051.9 9.856121 4.8051e−23 0.296511 0.179808 330 402 27238.686 RxP HcC 272.6 165.4 1046.7 9.080465 7.9710e−20 0.260438 0.158052304 346 264 43.163 GLP CCC 279.5 169.6 1833.1 8.854745 6.0139e−190.152474 0.092541 296 355 249 50.76 SxxxT HhhhH 386.1 234.4 2954.610.3294 3.6971e−25 0.130678 0.079323 398 462 317 75.756 TxS ChH 302.5183.7 1336.5 9.440319 2.7128e−21 0.226337 0.13743 310 375 236 52.207 NxEChH 840.2 510.2 3189.6 15.94033 2.4469e−57 0.263419 0.159957 852 1054677 130.26 DxxE ChhH 635.3 386.1 2788.7 13.66215 1.2445e−42 0.2278120.138458 672 790 548 102.326 QxxxV HhhhH 290.2 176.4 3024.7 8.8299367.4024e−19 0.095943 0.058319 316 371 260 85.71 GxV CcH 142.7 86.8 982.26.289195 2.2883e−10 0.145286 0.088337 147 166 125 31.929 PxA ChH 300.2182.7 1377.9 9.335371 7.3154e−21 0.217868 0.132582 316 363 256 49.987RxxQ HhhH 1120.7 683.5 5021.1 17.99374 1.5808e−72 0.223198 0.13612 10941312 857 202.148 NxS ChH 286.4 174.8 1258.8 9.10101 6.5075e−20 0.2275180.138825 303 357 250 54.56 LPP CCC 180.4 110.2 1229.1 7.0149721.6415e−12 0.146774 0.08962 178 217 156 21.42 RxN EeC 190.4 116.3 798.37.437105 7.5124e−14 0.238507 0.145653 179 217 124 38.991 IxxxK HhhhH702.9 429.8 5778.4 13.69065 8.1501e−43 0.121643 0.074385 777 874 600134.385 QxxH HhhH 240 146.8 1371.3 8.139332 2.8477e−16 0.175016 0.107058250 298 214 48.318 RxQ EeE 235.1 143.8 1065.2 8.180894 2.0416e−160.22071 0.135042 232 277 172 39.053 DxxxE HhhhH 1501.2 918.8 7072.820.59983 1.9838e−94 0.21225 0.129901 1488 1867 1173 279.838 NxxxG HhhhH155 94.9 1305.1 6.409783 1.0322e−10 0.118765 0.072698 175 191 155 33.083PxxG HhhC 153 93.7 807.5 6.509851 5.4137e−11 0.189474 0.11609 174 190141 20.911 DxxxA HhhhH 1305.7 800.2 8841.7 18.73718 1.7447e−78 0.1476750.090505 1347 1647 1120 211.68 LY HC 138.9 85.1 796.1 6.1659635.0248e−10 0.174476 0.106941 152 170 121 14.864 PxxL ChhH 222.4 136.42084.4 7.621642 1.7634e−14 0.106697 0.065419 243 272 201 46.144 VxxxFHhhhH 171.5 105.2 4285.6 6.549046 4.0245e−11 0.040018 0.02454 169 218145 84.989 DxS CcE 237.4 145.6 1171.4 8.130164 3.0858e−16 0.2026630.124293 257 272 120 29.903 ExxLE HhhHH 164.2 100.8 1515.9 6.5396724.3457e−11 0.108318 0.066476 182 196 160 35.833 NxxP HhcC 135.6 83.2 6556.145038 5.7748e−10 0.207023 0.127058 159 177 133 25.879 QxG HcC 492.4302.3 1853.5 11.95146 4.6538e−33 0.26566 0.163098 546 659 433 83.868AxxxL HhccC 142.7 87.6 1446 6.06968 9.0182e−10 0.098686 0.060602 188 204166 29.997 TxP HcC 196.8 121 877.5 7.425272 8.1367e−14 0.224274 0.137858217 250 174 33.337 ALP CCC 144.5 88.8 974.8 6.194927 4.1448e−10 0.1482360.091132 150 179 129 30.435 YxxG HhcC 182 111.9 1042.3 7.0124161.6727e−12 0.174614 0.10737 183 215 149 52.14 DxxT ChhH 458.9 282.22519.2 11.16131 4.4957e−29 0.182161 0.112025 479 585 405 89.773 YxF CcC231.3 142.3 1699 7.788873 4.7756e−15 0.136139 0.083784 249 268 17383.115 SxxA ChhH 337.5 207.7 2881.5 9.347949 6.2762e−21 0.1171260.072087 377 424 299 84.421 FxI EeE 196.6 121 5105.9 6.953154 2.4724e−120.038504 0.023702 213 219 156 66.504 DxxN ChhH 214.4 132 1123.3 7.6334531.6354e−14 0.190866 0.117519 239 297 184 64.208 DxxA ChhH 593.4 365.53282 12.64821 8.1426e−37 0.180804 0.111354 630 744 513 75.148 LxL CcH176.2 108.5 1561.1 6.732965 1.1688e−11 0.112869 0.069526 189 207 15535.143 IxxxY HhhhH 164.9 101.6 3264 6.374812 1.2709e−10 0.050521 0.03114176 198 154 46.701 KxxG HhhC 867.2 534.5 3433.8 15.65894 2.0892e−550.252548 0.155669 924 1110 716 134.251 FxS EeE 172.8 106.5 2333 6.5718213.4634e−11 0.074068 0.045664 180 194 131 54.814 QH HC 145.4 89.7 4246.630426 2.4996e−11 0.342925 0.211441 164 184 139 29.8 TxxxxE ChhhhH224.8 138.7 1943.5 7.580991 2.4056e−14 0.115668 0.071391 268 281 21737.067 AxxKA HhhHH 166.5 102.8 1820.9 6.469686 6.8625e−11 0.0914380.056448 206 240 174 25.798 QxxQ HhhH 966 596.4 4465.5 16.256541.4369e−59 0.216325 0.133567 947 1146 759 157.719 PxxxxR HhhhhH 238.9147.5 2305.1 7.777629 5.1670e−15 0.10364 0.063993 272 286 215 41.213AxxxY HhhhH 328.5 202.9 5012.4 9.005726 1.4841e−19 0.065537 0.040471 339400 304 88.415 GxxG HhhC 171.9 106.2 1065.7 6.724762 1.2479e−11 0.1613020.099611 215 221 165 33.951 WxxR HhhH 186.9 115.5 1454.6 6.9295542.9705e−12 0.128489 0.079374 197 238 151 72.73 YxP EcC 223.8 138.31582.3 7.610135 1.9299e−14 0.14144 0.087407 250 288 204 54.263 TxxxxKChhhhH 195.3 120.8 1644.2 7.037027 1.3767e−12 0.118781 0.073495 229 240181 47.354 SxL HhC 258 159.7 1828 8.14081 2.7616e−16 0.141138 0.087371307 339 232 50.261 FxY CcC 197.6 122.3 1387.8 7.126119 7.2715e−130.142384 0.088151 205 232 151 68.212 PxA CcH 167.1 103.6 1215 6.5280794.6873e−11 0.137531 0.085236 193 221 168 47.747 ExxY HhhH 594.3 368.64092.2 12.32158 4.8612e−35 0.145228 0.090082 630 705 509 120.715 EH HC228.4 141.7 666.7 8.20849 1.6592e−16 0.342583 0.212529 233 279 20242.365 HxE ChH 196.5 121.9 874.7 7.277859 2.4319e−13 0.224648 0.139413202 236 160 30.705 SxV ChH 170.8 106 1130.6 6.610197 2.7051e−11 0.151070.093764 179 206 139 31.222 FG HC 520.5 323.3 2395.3 11.79391 2.9912e−320.217301 0.134962 589 673 478 92.261 PxE ChH 750.1 466 2940 14.345888.1316e−47 0.255136 0.158508 757 942 616 106.696 YN HC 175.1 108.8 647.76.965652 2.3708e−12 0.270341 0.168011 195 225 138 30.624 TxxG HhcC 231.4144.2 1143.9 7.77065 5.5443e−15 0.20229 0.126037 253 305 199 42.592 PGDCCC 199.2 124.2 1125.9 7.138468 6.6622e−13 0.176925 0.110285 217 252 15638.178 KxxxP HhhcC 278.6 173.7 1410.7 8.496381 1.3851e−17 0.1974910.123154 307 370 236 49.368 SxG EeC 176.7 110.2 1436.4 6.591013.0464e−11 0.123016 0.076729 189 214 121 62.904 FxxE HhhH 477.3 297.74177.8 10.79934 2.4039e−27 0.114247 0.071263 503 577 429 90.405 PGA CCC212.4 132.7 1275.2 7.304192 1.9593e−13 0.166562 0.104098 240 269 17062.409 DxD ChH 676.9 423.4 2579 13.47793 1.5116e−41 0.262466 0.164158678 857 564 112.944 AxP HcC 365.8 228.9 1699.7 9.723656 1.6933e−220.215214 0.134695 409 472 349 60.063 NxL HhC 178 111.4 1250.4 6.6093122.6962e−11 0.142354 0.089105 216 254 182 29.912 NxT ChH 211 132.2 9677.375862 1.1589e−13 0.218201 0.136714 220 273 175 54.286 RxxE HhhH2176.8 1363.9 9113.5 23.87027 4.4302e−126 0.238854 0.149656 2059 26381645 369.823 PLP CCC 188.1 117.9 1190.8 6.8156 6.5703e−12 0.1579610.098979 204 232 172 26.197 EAxxR HHhhH 158.7 99.5 1610.8 6.1307626.0465e−10 0.098522 0.061753 167 191 161 19.566 KxxxxE HhhccC 156.1 97.91140.5 6.155009 5.2325e−10 0.13687 0.08582 191 208 161 16.66 SxxN HhhH444.5 278.8 2709 10.47981 7.4674e−26 0.164083 0.102906 464 532 373113.319 NxxA HhhH 615.2 385.8 4642 12.19475 2.2966e−34 0.132529 0.083118635 762 475 113.773 RxL EeC 168.4 105.6 952.5 6.475264 6.6512e−110.176798 0.110913 191 218 147 40.276 NxG HcC 306.9 192.6 1423.3 8.8599075.6640e−19 0.215626 0.135299 345 401 287 66.643 DxA EcC 185.1 116.1 12476.718472 1.2812e−11 0.148436 0.093142 190 220 143 27.415 GF CE 273.1171.4 2043.3 8.118336 3.2802e−16 0.133656 0.083872 291 321 212 77.768LxxxL HhhhH 997.1 625.8 27017.2 15.01725 3.8391e−51 0.036906 0.023163982 1113 809 274.286 ExxxQ HhhcC 146.5 92 726.3 6.086124 8.1812e−100.201707 0.12661 180 200 153 18.605 FG EC 205.6 129.1 2232.1 6.9380622.7367e−12 0.092111 0.057832 230 269 170 66.387 TxA EcC 184.9 116.21173.5 6.718406 1.2831e−11 0.157563 0.098991 207 238 151 28.363 SxxPHhcC 304.6 191.7 1389.7 8.784923 1.1050e−18 0.219184 0.137925 344 403238 54.435 YxE EeE 316.8 199.4 2122.7 8.730258 1.7640e−18 0.1492440.093957 332 360 245 78.824 DxT ChH 325.9 205.3 1490.9 9.0643518.8406e−20 0.218593 0.1377 337 422 287 58.774 SxG HhC 349.5 220.3 1705.19.325761 7.7389e−21 0.204973 0.129216 423 481 340 54.017 TxL ChH 162.1102.2 1235.2 6.186318 4.2666e−10 0.131234 0.082742 169 187 128 40.459TxxR HhhH 765 482.3 4295 13.66071 1.2139e−42 0.178114 0.1123 802 918 592168.53 VxxxK HhhhH 731.6 461.5 5991.9 13.08537 2.7448e−39 0.1220980.077025 816 955 651 134.532 SxxxL HhhhH 397 250.5 6529.4 9.4368292.6110e−21 0.060802 0.038369 451 505 397 101.928 YxY CcC 288.7 182.31760.3 8.320026 6.1115e−17 0.164006 0.10358 293 340 185 93.01 YxxxAHhhhH 236.1 149.1 3917.6 7.260707 2.6193e−13 0.060266 0.038068 270 300229 57.862 QxxL HhhH 1100.1 695.9 9726.7 15.90009 4.3300e−57 0.1131010.071549 1109 1293 900 204.094 SxxxxE ChhhhH 255.8 161.8 2369.5 7.6531271.3452e−14 0.107955 0.068296 294 334 245 39.409 HxD ChH 172.1 108.9762.7 6.538917 4.3732e−11 0.225646 0.142806 177 217 150 51.532 RxxN HhhC163.9 103.7 766.6 6.352558 1.4905e−10 0.213801 0.135319 196 217 16828.434 NxxxK HhhhH 677.6 429.3 3506.7 12.79517 1.2149e−37 0.193230.122411 705 832 558 129.092 AxxxG HhhhH 369.9 234.4 5304.5 9.0495129.7444e−20 0.069733 0.044196 418 481 332 62.946 DxxI HhhH 616.4 390.75172.8 11.87378 1.1089e−32 0.119162 0.075536 671 756 543 110.773 NxD ChH495.1 313.9 2040 11.12133 6.9636e−29 0.242696 0.153854 510 643 41484.876 SxD ChH 668.8 424.4 2701 12.92494 2.2948e−38 0.247612 0.157111682 847 535 117.318 SxxS ChhH 231.8 147.1 1773.6 7.288639 2.1527e−130.130695 0.082959 256 295 197 65.521 DxxxR ChhhH 322.4 204.7 1923.28.701026 2.2763e−18 0.167637 0.106447 347 378 250 52.532 QxxF HhhH 273.6173.9 2934.2 7.798778 4.2571e−15 0.093245 0.059253 289 316 237 60.216DxxxL HhhhH 575.4 366.1 6298.7 11.27182 1.2269e−29 0.091352 0.058122 643702 516 117.811 FxxR HhhH 351 223.5 3213.2 8.837814 6.6518e−19 0.1092370.06957 379 434 315 101.994 RxxA HhhC 210.3 134 1114.3 7.0294781.4404e−12 0.188728 0.120238 264 288 217 41.829 RxxxK HhhhH 1047 667.35094.2 15.76929 3.5148e−56 0.205528 0.130986 1109 1350 881 229.876 HxxDHhhH 233.8 149 1324.2 7.369841 1.1824e−13 0.176559 0.112552 244 288 20145.746 ExxxP HhhcC 195.4 124.6 1156.3 6.718992 1.2654e−11 0.1689870.107727 227 263 200 41.813 KxxxE HhhhH 2766.8 1765.1 13152.5 25.624915.5898e−145 0.210363 0.1342 2615 3468 1999 431.109 TxxN HhhH 437.5 279.12805.4 9.989921 1.1590e−23 0.155949 0.099494 452 523 353 80.127 QxG HhC389.7 248.6 1652.1 9.705388 2.0025e−22 0.235882 0.150503 468 545 38468.89 TxD ChH 596.6 380.9 2366.4 12.06539 1.1295e−33 0.252113 0.160964614 769 469 103.233 ExxG EecC 416.3 266 2056.9 9.876549 3.6490e−230.202392 0.129319 418 505 320 71.375 FxxxA HhhhH 223.3 142.7 5346.26.83435 5.5321e−12 0.041768 0.0267 248 306 218 78.557 LxxxF HhhhH 296.1189.7 7589.4 7.81986 3.5385e−15 0.039015 0.025001 334 359 275 99.347 RxGHcC 600.4 385.3 2430.5 11.94617 4.7458e−33 0.247027 0.158526 649 770 56599.981 DxL ChH 284.2 182.4 1624.1 8.001921 8.4214e−16 0.174989 0.112298276 344 233 62.639 PGxP CCcC 176.6 113.4 1196.2 6.242508 2.9487e−100.147634 0.094769 184 218 139 29.145 DxG HcC 432.5 277.7 1780.1 10.113183.3685e−24 0.242964 0.15599 473 585 397 65.071 DxG HhC 361.9 232.41588.1 9.195611 2.5922e−20 0.227882 0.146327 420 495 336 60.8 RxxN HhhH493 316.8 2440.1 10.61521 1.7471e−26 0.202041 0.129815 501 583 395101.528 AxxQ HhhH 1213 780.1 7792 16.34001 3.4909e−60 0.155672 0.1001121229 1452 953 204.164 ExxN HhhH 1108.5 713.4 5126.3 15.94207 2.2333e−570.216238 0.13917 1069 1307 840 232.803 DxV ChH 274.2 176.5 1472.47.839595 3.1082e−15 0.186227 0.119867 292 321 232 52.187 TxxxG EcccC266.6 171.7 1990.3 7.577823 2.3879e−14 0.13395 0.086262 296 340 24561.191 AxV CeE 213.1 137.3 2617.4 6.642462 2.0749e−11 0.081417 0.052467243 276 193 40.286 ExxKR HhhHH 190.5 122.9 1294.5 6.413164 9.7168e−110.147161 0.094917 220 245 190 33.813 SxL ChH 229.3 147.9 1709.6 7.0017591.7166e−12 0.134125 0.086519 245 278 192 47.142 DxP ChH 163.2 105.3784.1 6.063957 9.1857e−10 0.208137 0.134297 175 196 132 27.338 AxG HhC719.4 465.5 3596.3 12.61434 1.2059e−36 0.200039 0.12943 843 967 694130.922 QxxA HhhH 1224.8 792.5 8547.3 16.12184 1.2114e−58 0.1432970.092719 1219 1484 974 208.072 PxxxL HhhhH 274.8 178.1 3402.7 7.4459086.4391e−14 0.080759 0.052333 312 341 258 76.433 GAD CCC 214.2 138.81524.5 6.711627 1.3044e−11 0.140505 0.091053 221 284 180 35.942 RxT EeC180.5 117.1 856 6.301282 2.0319e−10 0.210864 0.136844 190 211 127 41.096IxQ EeE 206.3 134 2177 6.450579 7.4700e−11 0.094763 0.061539 224 231 17852.446 PxxxK HhhhH 653.9 424.7 3404.9 11.88889 9.2174e−33 0.1920470.124727 683 814 550 106.479 DGR CCC 235.9 153.2 1180.8 7.159785.5359e−13 0.19978 0.129763 266 295 185 31.236 YH HH 259.5 168.6 1432.67.45738 6.0182e−14 0.181139 0.117657 236 291 175 73.31 PxxL HhhH 608.9395.6 6143.7 11.08991 9.3855e−29 0.09911 0.064384 643 716 482 107.923RxxG HhcC 659.6 428.8 2824.2 12.10492 6.8433e−34 0.233553 0.151816 731878 617 99.95 ExY EeE 264 171.7 2049.9 7.357882 1.2583e−13 0.1287870.083765 278 310 235 72.719 DxxQ HhhH 723.6 471.1 3555.4 12.487685.9445e−36 0.203521 0.132515 770 883 627 128.257 LxxE HhhH 1464.3 953.512363.8 17.21774 1.3074e−66 0.118434 0.077123 1431 1679 1159 242.872ExxG HhcC 744.6 484.9 3281.4 12.77534 1.5440e−37 0.226915 0.147772 841980 713 126.74 ExxxE HhhhC 174.4 113.6 865.2 6.122948 6.2923e−100.201572 0.131275 217 256 201 29.344 VxP CcH 241 157.2 1873.4 6.9805281.9763e−12 0.128643 0.083925 283 319 238 39.774 AS HC 387 252.5 1734.39.157518 3.6376e−20 0.223145 0.145589 431 493 330 68.227 TxxD ChhH 532.6347.6 3154.7 10.52015 4.7150e−26 0.168827 0.11018 570 661 449 96.783 KxGHhC 794.3 518.5 3293.5 13.19624 6.3329e−40 0.241172 0.157426 873 1027674 123.629 TxK ChH 363.6 237.5 1518.2 8.90932 3.5284e−19 0.2394940.156432 358 438 263 46.819 YxR EeE 222.6 145.4 1667.1 6.6973941.4262e−11 0.133525 0.087238 235 256 181 62.069 ExxxK HhhhH 3252.32124.9 15568.8 26.31791 8.1352e−153 0.208899 0.136488 2973 4024 2223531.075 LxxxI HhhhH 431.1 282 13352.3 8.970538 1.9380e−19 0.0322870.021123 457 511 375 146.35 CxA CcC 240 157.1 1719.3 6.936502 2.6998e−120.139592 0.091386 251 295 175 79.348 QxxV HhhH 486.1 318.5 4621.89.73421 1.4329e−22 0.105175 0.068907 514 576 420 74.196 NxxK ChhH 267.5175.3 1255.7 7.503694 4.2292e−14 0.213029 0.139633 301 336 254 43.698ExxL HhhC 231.1 151.5 1603.1 6.7972 7.1660e−12 0.144158 0.094498 281 317238 41.927 PGT CCC 187.5 122.9 1179.6 6.152747 5.1368e−10 0.1589520.104216 207 228 155 38.844 SxxxK HhhhH 834.7 547.3 4847.5 13.044134.6206e−39 0.172192 0.112901 874 1041 709 151.146 QxxS HhhH 573.5 376.23395 10.78583 2.7025e−27 0.168925 0.110817 610 690 489 100.464 RxG HhC536.7 352.1 2365.3 10.66383 1.0247e−26 0.226906 0.148858 591 683 52390.687 KH HC 254.7 167.1 760.9 7.669848 1.2101e−14 0.334735 0.219625 272327 207 55.477 DxQ CcE 200.1 131.3 843.7 6.532723 4.4296e−11 0.237170.155639 228 251 167 22.113 ExxN HhhC 219.4 144 1018.4 6.7789348.2548e−12 0.215436 0.141417 266 312 235 36.571 GP EE 210.9 138.4 1127.36.574937 3.2980e−11 0.187084 0.12281 208 255 159 43.308 ExH EeE 193.8127.3 1158.7 6.249782 2.7732e−10 0.167256 0.109845 210 230 172 59.385IxY EeE 243 159.7 3724.8 6.738568 1.0556e−11 0.065238 0.042872 281 307206 68.244 TS CH 275.6 181.2 1047.3 7.71034 8.6337e−15 0.263153 0.173029270 302 172 48.603 AA HC 564.4 371.6 2472.5 10.85223 1.3234e−27 0.2282710.150281 617 755 525 87.719 HxxxA HhhhH 224.3 147.7 2542.3 6.4919955.6070e−11 0.088227 0.058106 255 282 222 55.81 RxS EeC 232.6 153.21206.4 6.864615 4.5085e−12 0.192805 0.126997 243 291 130 99.543 AxP CcH300.6 198.2 1840.7 7.701465 9.0209e−15 0.163307 0.107667 349 397 27955.725 AxxP HhcC 384.9 253.9 1977.2 8.806219 8.7288e−19 0.1946690.128413 430 503 365 64.191 AxxG HhcC 596.4 393.6 3729.4 10.811492.0296e−27 0.159918 0.105527 706 816 603 104.595 VxxxS HhhhH 240.9 1593366.1 6.65677 1.8435e−11 0.071567 0.047228 286 320 238 57.927 GxF CcE309.7 204.4 2645.7 7.664502 1.1912e−14 0.117058 0.07727 359 372 24773.042 AxN HcC 206.2 136.2 1076.8 6.420579 9.1640e−11 0.191493 0.126461233 274 193 36.263 QxxK HhhH 1225.8 809.9 5705.9 15.77567 3.0884e−560.21483 0.141944 1252 1543 971 183.382 SxY EeE 224.1 148.1 2359.26.447301 7.5251e−11 0.09499 0.06279 259 270 162 64.803 DxDG CcCC 197.6130.7 1653 6.102896 6.9206e−10 0.11954 0.079041 179 191 98 30.41 AxxxECchhH 196.6 130 1472.9 6.114589 6.4488e−10 0.133478 0.088278 231 266 19334.905 KxxxL HhhhH 975 645.5 8499.3 13.48896 1.1986e−41 0.1147150.075953 1031 1221 860 169.471 TxH EeE 235.2 155.8 1626.2 6.6913611.4731e−11 0.144632 0.095796 262 288 193 60.839 YxxT HhhH 223.7 148.32165.8 6.417924 9.1255e−11 0.103287 0.068461 239 265 193 48.734 SA CH566.6 375.7 2576.3 10.65475 1.1178e−26 0.219928 0.145839 552 686 411118.754 DxxN HhhH 709.7 470.7 3574.6 11.82169 2.0234e−32 0.19854 0.13168758 884 582 111.272 RxG EeC 261.5 173.5 1393.1 7.141804 6.1825e−130.187711 0.124531 263 313 216 70.077 ExxL HhhH 2067.7 1372.8 16331.319.59683 1.0853e−85 0.12661 0.084059 2024 2416 1566 366.474 DxT EcC210.2 139.6 1345.2 6.313609 1.8180e−10 0.156259 0.103764 231 261 17542.758 GVP CCC 226.5 150.5 1776.5 6.477441 6.1803e−11 0.127498 0.084706271 290 172 35.726 NxxE HhhH 551.2 366.4 2767 10.36368 2.4310e−250.199205 0.132425 569 681 482 93.396 QxxP HhcC 214.3 142.7 978 6.4903395.7784e−11 0.219121 0.145866 252 286 217 34.293

What is claimed is:
 1. A method for increasing the number ofhigh-quality crystal-packing motifs in a target protein to improve itscrystallization properties, comprising: a. providing a sub-epitopelibrary containing local crystal-packing motifs in the PDB that span atmost two-successive regular secondary structural elements and flankingloops, wherein each sub-epitope is ranked by p-value according to itsoverrepresentation in crystal-packing interfaces formed by crystalstructures in the PDB that do not have excessively close inter-proteincontacts; b. identifying one or more specific candidate sites in thesequence of the target protein for introduction of each sub-epitope inthe library by: i. using a computer program to search a protein sequencedatabase for proteins homologous to the target protein; ii. using acomputer program to perform a multiple sequence alignment of the targetsequence with the homologous proteins identified by the search program;iii. using a computer program to predict the secondary structure of thetarget protein based on its sequence; and iv. specifying exact sites inthe target protein for introduction of a sub-epitope from the librarybased on the occurrence of residues similar to those in the sub-epitopeat aligned positions in one of the homologous protein sequences and onconservation of the secondary structure of the sub-epitope in the targetprotein; and c. prioritizing sub-epitopes for introduction viamutagenesis at the specific sites identified for that sub-epitope in thetarget protein based on the overrepresentation p-value of thesub-epitope in crystal-packing interfaces; and d. further prioritizingsub-epitopes for introduction via mutagenesis at the specific sitesidentified for that sub-epitope in the target protein based on whetherthe number of sub-epitopes of equal or better overrepresentation p-valueis increased by the required mutations in the target sequence; and e.obtaining a mutant protein sequence of the target protein based on thesub-epitope prioritization steps and wherein the mutant protein sequenceis expressed in an expression system.
 2. The method of claim 1 in whichthe sub-epitope library comprises the sequences in tables 1-38.
 3. Themethod of claim 1, in which the candidate sub-epitopes for substitutionat the candidate sites is selected from tables 8 or
 12. 4. A method forincreasing the number of high-quality crystal-packing motifs in a targetprotein to improve its crystallization properties comprising: a.providing a sub-epitope library containing local crystal-packing motifsin the PDB that span at most two-successive regular secondary structuralelements and flanking loops, wherein each sub-epitope is ranked byp-value according to its overrepresentation in crystal-packinginterfaces formed by crystal structures in the PDB that do not haveexcessively close inter-protein contacts; b. identifying one or morespecific candidate sites in the sequence of the target protein forintroduction of each sub-epitope in the library by: i. using a computerprogram to search a protein sequence database for proteins homologous tothe target protein; ii. using a computer program to perform a multiplesequence alignment of the target sequence with the homologous proteinsidentified by the search program; iii. using a computer program topredict the secondary structure of the target protein based on itssequence; and iv. specifying exact sites in the target protein forintroduction of a sub-epitope from the library based on the occurrenceof residues similar to those in the sub-epitope at aligned positions inone of the homologous protein sequences and on conservation of thesecondary structure of the sub-epitope in the target protein; and c.prioritizing sub-epitopes for introduction via mutagenesis at thespecific sites identified for that sub-epitope in the target proteinbased on the overrepresentation p-value of the sub-epitope incrystal-packing interfaces; and d. further prioritizing sub-epitopes forintroduction via mutagenesis at the specific sites identified for thatsub-epitope in the target protein based on whether the number ofsub-epitopes of equal or better overrepresentation p-value is increasedby the required mutations in the target sequence; and e. obtaining amutant protein sequence of the target protein based on the sub-epitopeprioritization steps and wherein the mutant protein sequence isexpressed in an expression system, and the expressed protein iscrystallized and its structure is determined with high-resolution X-raycrystallography.
 5. A method for increasing the number of high-qualitycrystal-packing motifs in a target protein to improve itscrystallization properties, comprising a. providing a sub-epitopelibrary containing local crystal-packing motifs in the PDB that span atmost two-successive regular secondary structural elements and flankingloops, wherein each sub-epitope is ranked by p-value according to itsoverrepresentation in crystal-packing interfaces formed by crystalstructures in the PDB that do not have excessively close inter-proteincontacts; b. identifying one or more specific candidate sites in thesequence of the target protein for introduction of each sub-epitope inthe library by: i. using a computer program to search a protein sequencedatabase for proteins homologous to the target protein; ii. using acomputer program to perform a multiple sequence alignment of the targetsequence with the homologous proteins identified by the search program;iii. using a computer program to predict the secondary structure of thetarget protein based on its sequence; and iv. specifying exact sites inthe target protein for introduction of a sub-epitope from the librarybased on the occurrence of residues similar to those in the sub-epitopeat aligned positions in one of the homologous protein sequences and onconservation of the secondary structure of the sub-epitope in the targetprotein; and c. prioritizing sub-epitopes for introduction viamutagenesis at the specific sites identified for that sub-epitope in thetarget protein based on the overrepresentation p-value of thesub-epitope in crystal-packing interfaces; and d. further prioritizingsub-epitopes for introduction via mutagenesis at the specific sitesidentified for that sub-epitope in the target protein based on whetherthe number of sub-epitopes of equal or better overrepresentation p-valueis increased by the required mutations in the target sequence; and e.obtaining a mutant protein sequence of the target protein based on thesub-epitope prioritization steps and wherein the mutant protein sequenceis expressed in an expression system to provide a mutant protein withthe mutant protein sequence and is crystallized and its structure isdetermined with high-resolution X-ray crystallography.
 6. The method ofclaim 5, in which the sub-epitope library comprises the sequences intables 1-38.
 7. The method of claim 5, in which the candidatesub-epitopes for substitution at the candidate sites is selected fromtables 8 or 12.